VOLUME 6 Regis Technologies ChiralChiral ApplicationApplication GuideGuide DURABLE, HIGH EFFICIENCY CHIRAL COLUMNS

ince 1980, Regis Technologies, Inc. has proven to be a leader in Schiral separations and services. Our support system to the analytical and preparative chromatographer is a model other manufacturers of chiral products try to emulate. Our technical expertise, professional staff, and worldwide distribution network is highly respected and praised in the chiral community.

Regis offers four different types of Chiral Stationary Phases (CSP’s): • Covalently bonded Pirkle-Type Concept • Protein-based • Covalently bonded 18 Crown-ether

The complete line of Pirkle-Type CSP’s are manufactured on-site at our cGMP facility in Morton Grove, Illinois. Columns range from analytical to preparative in size. Since Regis packs their own columns, custom sized columns are easily attainable.

All Regis Chiral Regis maintains an extended inventory of Protein-based columns Separations manufactured by ChromTech in the United Kingdom and the products must covalently bonded 18 Crown-Ether columns manufactured by RStech meet rigorous in South Korea. Information on these product lines is readily manufacturing and available on our website at www.registech.com. quality control specifications As evidence of our commitment to the scientist in the lab, Regis is before release. pleased to present its Chiral Application Guide VI. This new guide contains over 500 specific chiral applications using a variety of chiral column types. We have also included a few new sections in this guide. We added a Frequently Asked Question section and a Quick Scheme Method Development section.

For applications not listed in this guide, Regis maintains a dedicated chiral separations lab and chiral separations scientist. This enables Regis to offer a Free Chiral Screening Service to the scientific community. For specific column types, services or applications not listed in this guide, please contact Regis directly or visit our website for continuously updated information.

Regis Technologies, Inc.

1 CHIRAL HPLC APPLICATION GUIDE VI

CONTENTS Advantages of the Pirkle-Type Chiral Stationary Phases 3 Introduction to Regis Chiral Stationary Phases 4 Pirkle Chiral Stationary Phases Protein-based Chiral Stationary Phases RStech Corporation ChiroSil® RCA(+) and SCA(-) 18 Crown-Ether Chiral Stationary Phases Regis HPLC Chiral Column Product List 7 Aryl Propionic Acid Non Steroidal Anti-Inflammatory Drugs (NSAIDS) 8 Other Carboxylic Acids 11 Basic Nitrogen 15 Basic Amine 15 Esters, Lactones, Ketones, Anhydrides 16 Amides, Imides, Carbamates, etc. 20 Epoxides 24 Alcohols 25 Diols, Hydroxyketones, etc. 32 Sulfoxides 33 Phosphorous Compounds 36 Atropisomers 39 Optical Switches, Liquid Crystal Components 47 Allenes 48 Organometallic Compounds 53 Agricultural Compounds 56 Miscellaneous Pharmaceuticals 61 Barbiturates, Ureas and Diol Epoxides 74 Natural Products 75 β-Blockers 76 Amino Acids 79 Frequently Asked Questions 82 Quick Scheme Method Development 83 References 86 Index 87 Applications by Compound Applications by Column Type Chiral Screening Data Sheet 91

2 Advantages of the Pirkle-Type Chiral Stationary Phases

Universal Solvent Capability The entire family of Regis’ Pirkle-Type Chiral Stationary Phases (CSP’s) can be used in BOTH normal and reversed-phase solvents. Due to the fact that all of the Pirkle-Type CSP’s are covalently bonded, the columns can tolerate all commonly used mobile phase combinations.

Column Durability Another advantage of covalent bonding is column durability. Listed below are a few distinct benefits associated with the Pirkle-Type CSP’s: • Long lasting columns • Bonded selector will not leach off the silica gel • Can tolerate sample overload • Can utilize strong solvents for cleaning • Columns are fully reversible • Compatible in SFC and SMB applications

Ability to Invert Elution Order All of the Pirkle-Type CSP’s are available in both enantiomeric forms. This allows the Chromatographer to invert the elution order of the enantiomers by simply switching columns. This advantage is essential when determining enantiomeric purity when the trace enantiomer should elute before the major. Elution order is also important in preparative chromatography because when the desired enantiomer elutes first, purity and production efficiency increases.

Chromatographic Efficiency Unlike most Chiral columns on the market, Pirkle-Type Chiral HPLC columns show excellent chromatographic efficiency. The high density of binding sites allows larger amounts of sample to be injected without major changes in column performance.

Ease of Scale-up Pirkle-Type CSP’s were designed to allow the Chromatographer to scale-up their separation from analytical to preparative in a linear fashion. Regis uses the highest grade silica gels available on the market today. The 5-micron CSP’s are bonded on Exsil®. Our 10-micron and 16-micron CSP’s are bonded on Kromasil®. Synthesis of the chiral selectors, bonding of the different CSP’s, and column production is all performed by Regis in one facility. This allows Regis total control over the product line. This also allows Regis to perform special requests for the customer, including custom bonding and custom column packing.

Regis Technologies, Inc.

3 REGIS Introduction to Regis Chiral Stationary Phases

Pirkle Chiral Stationary Phases The Pirkle-Concept Chiral Stationary Phases generally fall into three classes: π-electron acceptor/π-electron donors, the π-electron acceptors and the π-electron donors. With Pirkle Phases, chiral recognition occurs at binding sites. Major binding sites are classified as π-basic or π-acidic aromatic rings, acidic sites, basic sites, and steric interaction sites. Aromatic rings are potential sites for π-π interactions. Acidic sites supply hydrogens for potential intermolecular hydrogen bonds-the hydrogen is often an amido proton (N-H) from an amide, carbamate, urea, or amine. Basic sites, such as π- electrons, sulfinyl or phosphinyl oxygens, and hydroxy or ether oxygens, may also be involved in hydrogen bond formation. Steric interactions may also occur between large groups.

π-Electron Acceptor/π-Electron Donor Phases • WHELK-O 1 • WHELK-O 2 • ULMO

The latest and most revolutionary addition to the Pirkle-Concept series is the π-electron Whelk-O 1 acceptor/π-electron donor phase. This concept is an innovative incorporation of both π-acceptor and π-donor characteristics, resulting in a phase that can be used for a wide variety of compound groups.

WHELK-O 1 The Whelk-O 1 Chiral Stationary Phase is based on 1-(3,5-Dinitrobenzamido)- 1,2,3,4,-tetrahydrophenanthrene. This phase allows separation of underivatized racemates from a number of families including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, and alcohols. The Whelk-O 1 was originally designed for the separation of underivatized non- steroidal anti-inflammatory drugs (NSAIDs). This π-electron acceptor/π-electron donor phase exhibits an extraordinary degree of generality, allowing resolution of a wide variety of underivatized racemates. This broad versatility observed on the Whelk-O 1 column, compares favorably with polysaccharide-derived chiral stationary phases. In addition, because of the Whelk-O 1’s covalent nature, this chiral phase is compatible (S) with all commonly used mobile phases, including aqueous systems-a distinct advantage (S,S) (R) (S,S) over polysaccharide-derived chiral stationary phases. Other advantages include more stable less stable column durability, excellent efficiency, elution order inversion allowing availability of adsorbate adsorbate both enantiomeric forms, and excellent preparative capacity.

a) b) Tetrahydro- phenanthrene H-bond acceptor π system

H-bond donor

Conjugated π-system D Dinitrobenzamide N π-system B

a) Schematic diagram showing key b) Schematic diagram showing functional groups of the Whelk-O 1 generalized structure of analytes which involved in chiral recognition. are resolved on the Whelk-O 1.

4 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Introduction to Regis Chiral Stationary Phases REGIS

WHELK-O 2 The Whelk-O 2 is the covalent trifunctional version of the Whelk-O 1. The Whelk-O 2 retains the same chiral selector but modifies the support to silica from a monofunctional linkage to a trifunctional. In most cases, the enantioselectivity remains the same allowing the separation of the analogous family of racemates as does the Whelk-O 1. Whelk-O 2 was designed to enhance the stability of the stationary phase due to hydrolysis while using strong organic modifiers such as trifluoroacetic acid. The Whelk-O 2 is ideal for preparative separations since the material is bonded on 10 µm 100 Å spherical Kromasil silica. This allows the preparative chromatographer to Whelk-O 2 perform method development on their analytical column and immediately scale-up to larger diameter columns.

ULMO The ULMO chiral stationary phase was developed by Austrian Researchers, Uray, Lindner, and Maier. This CSP has a general ability to separate the enantiomers of many racemate classes, and is particularly good at separating the enantiomers of aryl carbinols.

The ULMO CSP is based on a 3,5-Dinitrobenzoyl derivative of diphenylethylene- ULMO diamine.

π-Electron Acceptor Phases • DACH-DNB • Pirkle 1-J • α-Burke 2 • β-Gem 1 • Leucine • Phenylglycine The π-electron acceptor Pirkle Chiral Stationary Phases can be used to separate a wide range of enantiomers without derivatization, as demonstrated for the following classes of solutes: secondary benzyl alcohols, mandelic acid analogs, α-hydroxy-α- aryl phosphates, α-tetralol analogs, propranolol analogs, β-hydroxy-aryl sulfoxides, alkyl-aryl sulfoxides, diaryl sulfoxides, aryl-substituted cyclic phthalides, aryl-substituted DACH-DNB lactams, aryl-substituted succinimides, aryl-substituted hydantoins, bi-β-naphthol and its analogs, and α-aryl acetamides.

DACH-DNB The innovative DACH-DNB CSP was designed by Italian chemists Dr. Francesco Gasparrini, Misiti and Villani at Rome University “La Sapienza.” The DACH-DNB CSP; which contains the 3,5-dinitrobenzoyl derivative of 1,2-diaminocyclohexane, has been found to resolve a broad range of racemate classes including amides, alcohols, esters, ketones, acids, sulfoxides, phosphine oxides, selenoxides, phosponates, thiophosphineoxides, phosphineselenides, phosphine-boranes, β-lactams, organo- metallics, atropisomers and heterocycles.

PIRKLE 1-J The Pirkle 1-J CSP is based on 3-(3,5-Dinitrobenzamido)-4-pheny-β-lactam. This unusual Pirkle 1-J β-lactam structure significantly alters its molecular recognition properties. The Pirkle 1J is useful for the direct separation of underivatized β-blocker enantiomers. It can also be used for the separation of the enantiomers of arylpropionic acid NSAID’s as well as other drugs.

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 5 REGIS Introduction to Regis Chiral Stationary Phases

α-BURKE 2 The α-Burke 2 phase, first prepared by J. A. Burke III, a graduate student of Dr. Pirkle, is derived from dimethyl N-3,5-dinitro-benzoyl-α-amino-2,2-dimethyl-4-pentenyl phosphonate. The α-Burke 2 has been specifically designed to directly separate the β α enantiomers of -blockers without chemical derivatization, but this chiral phase is not -Burke 2 limited solely to the separation of β-blocker enantiomers. It also resolves the enantiomers of many compounds separated on π-acceptor Pirkle type chiral stationary phases.

β-GEM 1 β-Gem 1 is a π-acceptor chiral stationary phase and is derived from N-3,5- dinitrobenzoyl-3-amino-3-phenyl-2-(1,1-dimethylethyl)-propanoate. For a great many analytes, this chiral phase considerably outperforms its widely used analog, phenylglycine. It can separate anilide derivatives of a wide variety of chiral β-Gem 1 carboxylic acids, including nonsteroidal anti-inflammatory agents.

LEUCINE The leucine CSP is based on the 3,5-dinitrobenzoyl derivative of leucine. This π-acceptor phase demonstrates enhanced enantioselectivities for several classes of compounds, including benzodiazapines.

PHENYLGLYCINE Leucine Phenylglycine is based on the 3,5-dinitrobenzoyl derivative of phenylglycine. This CSP resolves a wide variety of compounds which contain π-basic groups. These include: aryl-substituted cyclic sulfoxides, bi-β-naphthol and its analogs, α-indanol and α-tetralol analogs, and aryl-substituted hydantoins.

Protein-Based Chiral Stationary Phases Regis Technologies carries a line of protein-based chiral columns manufactured by Phenylglycine ChromTech AB, United Kingdom. For additional product information and a Protein-Based Chiral Stationary Phase application guide, please contact Regis directly. • Chiral AGP (α-glycoprotein) • Chiral CBH (cellobiohydrolase) • Chiral HSA (human serum albumin)

RStech Corporation ChiroSil® RCA(+) and SCA(-) 18Crown-Ether Chiral Stationary Phases • ChiroSil RCA(+) • ChiroSil SCA (-) Developed by RStech Corporation in Daejeon, Korea, the ChiroSil phase is the newest addition to our chiral line of columns. This phase is prepared by a covalent trifunctional ChiroSil bonding of (+) or (-)-(18-Crown-6)-tetracarboxylic acid as the chiral selector. This phase which is available in analytical as well as preparative columns, is an excellent choice for the separation of amino acids and compounds containing primary amines. Like our other line of columns, this phase is highly durable, has universal solvent compatibility, and has the ability to invert elution order.

As described above, Regis’ Chiral columns can be used to separate a wide variety of enantiomers in numerous compound groups. Please refer to the Product List on page 7 for particular column types, sizes, configurations and product numbers. Consult the application separation data section that begins on page 8 for information regarding specific chiral separations on a wide variety of compounds. See Application Indexes on page 87.

6 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Regis Chiral Column Product List REGIS

PRODUCT PARTICLE SIZE COLUMN DIMENSIONS PRODUCT# PRODUCT PARTICLE SIZE COLUMN DIMENSIONS PRODUCT#

(R,R)-Whelk-O 1 5 µm, 100 Å 25 cm x 4.6 mm 786201 (R,R)-DACH-DNB 5 µm, 100 Å 25 cm x 4.6 mm 788101 (R,R)-Whelk-O 1 5 µm, 100 Å 25 cm x 10.0 mm 786202 (R,R)-DACH-DNB 5 µm, 100 Å 25 cm x 10.0 mm 788102 (R,R)-Whelk-O 1 5 µm, 100 Å 25 cm x 30.0 mm 786205 (R,R)-DACH-DNB 5 µm, 100 Å 25 cm x 30.0 mm 788104 (S,S)-Whelk-O 1 5 µm, 100 Å 25 cm x 4.6 mm 786101 (S,S)-DACH-DNB 5 µm, 100 Å 25 cm x 4.6 mm 788201 (S,S)-Whelk-O 1 5 µm, 100 Å 25 cm x 10.0 mm 786102 (S,S)-DACH-DNB 5 µm, 100 Å 25 cm x 10.0 mm 788202 (S,S)-Whelk-O 1 5 µm, 100 Å 25 cm x 30.0 mm 786105 (S,S)-DACH-DNB 5 µm, 100 Å 25 cm x 30.0 mm 788204

(R,R)-Whelk-O 1 10 µm, 100 Å 25 cm x 4.6 mm 786515 (R,R)-DACH-DNB 10 µm, 100 Å 25 cm x 21.1 mm 788103 (R,R)-Whelk-O 1 10 µm, 100 Å 25 cm x 10.0 mm 786525 (R,R)-DACH-DNB 10 µm, 100 Å 25 cm x 30.0 mm 788707 (R,R)-Whelk-O 1 10 µm, 100 Å 25 cm x 21.1 mm 786535 (R,R)-DACH-DNB 10 µm, 100 Å 25 cm x 50.0 mm 788708 (R,R)-Whelk-O 1 10 µm, 100 Å 50 cm x 21.1 mm 786545 (R,R)-DACH-DNB 10 µm, 100 Å 50 cm x 30.0 mm 788712 (R,R)-Whelk-O 1 10 µm, 100 Å 25 cm x 30.0 mm 786708 (R,R)-DACH-DNB 10 µm, 100 Å 50 cm x 50.0 mm 788709 (R,R)-Whelk-O 1 10 µm, 100 Å 25 cm x 50.0 mm 786709 (S,S)-DACH-DNB 10 µm, 100 Å 25 cm x 21.1 mm 788203 (R,R)-Whelk-O 1 10 µm, 100 Å 50 cm x 30.0 mm 786713 (S,S)-DACH-DNB 10 µm, 100 Å 25 cm x 30.0 mm 788701 (R,R)-Whelk-O 1 10 µm, 100 Å 50 cm x 50.0 mm 786710 (S,S)-DACH-DNB 10 µm, 100 Å 25 cm x 50.0 mm 788702 (S,S)-Whelk-O 1 10 µm, 100 Å 25 cm x 4.6 mm 786615 (S,S)-DACH-DNB 10 µm, 100 Å 50 cm x 30.0 mm 788715 (S,S)-Whelk-O 1 10 µm, 100 Å 25 cm x 10.0 mm 786625 (S,S)-DACH-DNB 10 µm, 100 Å 50 cm x 50.0 mm 788705 (S,S)-Whelk-O 1 10 µm, 100 Å 25 cm x 21.1mm 786635 (S,S)-Whelk-O 1 10 µm, 100 Å 50 cm x 21.1 mm 786645 (3R,4S)-Pirkle 1-J 5 µm, 100 Å 25 cm x 4.6 mm 731044 (S,S)-Whelk-O 1 10 µm, 100 Å 25 cm x 30.0 mm 786702 (3R,4S)-Pirkle 1-J 5 µm, 100 Å 25 cm x 10.0 mm 731244 (S,S)-Whelk-O 1 10 µm, 100 Å 25 cm x 50.0 mm 786703 (3S,4R)-Pirkle 1-J 5 µm, 100 Å 25 cm x 4.6 mm 731045 (S,S)-Whelk-O 1 10 µm, 100 Å 50 cm x 30.0 mm 786716 (3S,4R)-Pirkle 1-J 5 µm, 100 Å 25 cm x 10.0 mm 731245 (S,S)-Whelk-O 1 10 µm, 100 Å 50 cm x 50.0 mm 786704 (R,R)-α-Burke 2 5 µm, 100 Å 25 cm x 4.6 mm 735035 (R,R)-Whelk-O 2 10 µm, 100 Å 25 cm x 4.6 mm 786315 (R,R)-α-Burke 2 5 µm, 100 Å 25 cm x 10.0 mm 735235 (R,R)-Whelk-O 2 10 µm, 100 Å 25 cm x 10.0 mm 786325 (S,S)-α-Burke 2 5 µm, 100 Å 25 cm x 4.6 mm 735037 (R,R)-Whelk-O 2 10 µm, 100 Å 25 cm x 21.1 mm 786335 (S,S)-α-Burke 2 5 µm, 100 Å 25 cm x 10.0 mm 735237 (R,R)-Whelk-O 2 10 µm, 100 Å 50 cm x 21.1 mm 786345 (R,R)-Whelk-O 2 10 µm, 100 Å 25 cm x 30.0 mm 786727 (R,R)-β-Gem 1 5 µm, 100 Å 25 cm x 4.6 mm 731043 (R,R)-Whelk-O 2 10 µm, 100 Å 25 cm x 50.0 mm 786728 (R,R)-β-Gem 1 5 µm, 100 Å 25 cm x 10.0 mm 731243 (R,R)-Whelk-O 2 10 µm, 100 Å 50 cm x 30.0 mm 786732 (S,S)-β-Gem 1 5 µm, 100 Å 25 cm x 4.6 mm 731029 (R,R)-Whelk-O 2 10 µm, 100 Å 50 cm x 50.0 mm 786729 (S,S)-β-Gem 1 5 µm, 100 Å 25 cm x 10.0 mm 731229 (S,S)-Whelk-O 2 10 µm, 100 Å 25 cm x 4.6 mm 786415 (S,S)-Whelk-O 2 10 µm, 100 Å 25 cm x 10.0 mm 786425 D-Leucine 5 µm, 100 Å 25 cm x 4.6 mm 731054 (S,S)-Whelk-O 2 10 µm, 100 Å 25 cm x 21.1mm 786435 D-Leucine 5 µm, 100 Å 25 cm x 10.0 mm 731254 (S,S)-Whelk-O 2 10 µm, 100 Å 50 cm x 21.1 mm 786445 L-Leucine 5 µm, 100 Å 25 cm x 4.6 mm 731041 (S,S)-Whelk-O 2 10 µm, 100 Å 25 cm x 30.0 mm 786721 L-Leucine 5 µm, 100 Å 25 cm x 10.0 mm 731241 (S,S)-Whelk-O 2 10 µm, 100 Å 25 cm x 50.0 mm 786722 (S,S)-Whelk-O 2 10 µm, 100 Å 50 cm x 30.0 mm 786736 D-Phenylglycine 5 µm, 100 Å 25 cm x 4.6 mm 731021 (S,S)-Whelk-O 2 10 µm, 100 Å 50 cm x 50.0 mm 786723 D-Phenylglycine 5 µm, 100 Å 25 cm x 10.0 mm 731221 L-Phenylglycine 5 µm, 100 Å 25 cm x 4.6 mm 731024 (R,R)-ULMO 5 µm, 100 Å 25 cm x 4.6 mm 787200 L-Phenylglycine 5 µm, 100 Å 25 cm x 10.0 mm 731224 (R,R)-ULMO 5 µm, 100 Å 25 cm x 10.0 mm 787201 (R,R)-ULMO 5 µm, 100 Å 25 cm x 30.0 mm 787203 Chiral AGP 5 µm, 300 Å 10 cm x 4.0 mm 732200 (S,S)-ULMO 5 µm, 100 Å 25 cm x 4.6 mm 787100 Chiral AGP 5 µm, 300 Å 15 cm x 4.0 mm 732199 (S,S)-ULMO 5 µm, 100 Å 25 cm x 10.0 mm 787101 Chiral CBH 5 µm, 300 Å 10 cm x 4.0 mm 732350 (S,S)-ULMO 5 µm, 100 Å 25 cm x 30.0 mm 787103 Chiral CBH 5 µm, 300 Å 15 cm x 4.0 mm 732351 Chiral HSA 5 µm, 300 Å 10 cm x 4.0 mm 732240 (R,R)-ULMO 10 µm, 100 Å 25 cm x 21.1 mm 787202 Chiral HSA 5 µm, 300 Å 15 cm x 4.0 mm 732239 (R,R)-ULMO 10 µm, 100 Å 25 cm x 30.0 mm 787707 (R,R)-ULMO 10 µm, 100 Å 25 cm x 50.0 mm 787708 ChiroSil® RCA(+) 5 µm, 100 Å 15 cm x 4.6 mm 799001 (R,R)-ULMO 10 µm, 100 Å 50 cm x 30.0 mm 787712 ChiroSil® RCA(+) 5 µm, 100 Å 25 cm x 4.6 mm 799002 (R,R)-ULMO 10 µm, 100 Å 50 cm x 50.0 mm 787709 ChiroSil® SCA(-) 5 µm, 100 Å 15 cm x 4.6 mm 799101 (S,S)-ULMO 10 µm, 100 Å 25 cm x 21.1 mm 787102 ChiroSil® SCA(-) 5 µm, 100 Å 25 cm x 4.6 mm 799102 (S,S)-ULMO 10 µm, 100 Å 25 cm x 30.0 mm 787701 (S,S)-ULMO 10 µm, 100 Å 25 cm x 50.0 mm 787702 Bulk material is available for all Chiral Stationary Phases (S,S)-ULMO 10 µm, 100 Å 50 cm x 30.0 mm 787715 (S,S)-ULMO 10 µm, 100 Å 50 cm x 50.0 mm 787703 For column dimensions not listed, please contact Regis

NOTE: All columns (except the protein-based columns) listed contain chiral stationary phases that are covalently bound on 5 µm or 10 µm 100 Å spherical silica. A large variety of column dimensions and/or particle sizes are available upon request.

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 7 REGIS Aryl Propionic Acid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ketoprofen Naproxen (semi prep) Ketoprofen Naproxen (semi prep on CH Column = (R,R)-Whelk-O 1 analytical column) 3 25 cm x 4.6 mm 80:20:0.5 hexane/IPA/HOAc OH Mobile Phase = (47/47/6) 1 ml/min; 300 nm CH2Cl2/Hexane/Ethanol + Run Time = 18 min H3C O 0.01 M Ammonium Acetate inject 400 µl @ O Flow Rate = 1.5 mL/min 31.5 mg/ml = 12.6 mg Detection = UV 254 nm 4.6 mm x 25 cm Whelk-O 1 Run Time = 11.0 min reference 6 k'1 = 3.63 α = 1.35 reference 46

Fenoprofen Etodolac Fenoprofen Etodolac Column = (R,R)-Whelk-O 1 Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98/2) Mobile Phase = (98/2) Hexane/IPA + Hexane/IPA + 0.1% TFA 0.1% Acetic Acid Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 14.5 min Run Time = 14.5 min k'1 = 2.43 k'1 = 2.62 α = 1.50 α = 1.66 reference 48 reference 46

Cicloprofen Tiaprofenic Acid Cicloprofen Tiaprofenic Acid 20% IPA/hex, 1g/L NH4OAc 20% IPA/hex, 1g/L NH4OAc 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 CH3 k'1 = 1.16 CH3 k' = 2.02 O α = 2.15 1 S OH α = 1.09 reference 4 OH reference 4 O O

Pirprofen Ketoprofen as 1-naphthylamide Pirprofen Column: (S,S)-ULMO 20% IPA/hex, 1g/L 25 cm x 4.6 mm NH4OAc CH Mobile Phase = (70/30) 2 ml/min; 254 nm 3 Heptane/IPA 4.6 mm x 25 cm Whelk-O 1 Cl OH Flow Rate = 1.0 mL/min k'1 = 0.85 Detection = UV 230 nm α = 1.81 O Run Time = 13 min reference 4 N k'1 = 1.51 α = 1.25 reference 48

8 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Aryl Propionic Acid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) REGIS Naproxen (R:S=30:70) Cicloprofen Column = (S,S)-ULMO Cicloprofen 25 cm x 4.6 mm 70:30:0.5 hexane/IPA/HOAc Mobile Phase (90/10) 1 ml/min; 254 nm Heptane/IPA + 0.1% TFA 4.6 mm x 25 cm Whelk-O 1 Flow Rate = 1.0 mL/min k' = 0.48 1 CH Detection = UV 230 nm α = 1.35 3 Run Time = 8.5 min reference 26 OH k'1 = 1.54 α = 1.34 O reference 48

Ibuprofen Naproxen (Reversed Phase) Ibuprofen Naproxen (Reversed Phase) Column = (R,R)-Whelko-O 1 Column = (R,R)-Whelko-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (90/10) Mobile Phase: (80/20) Hexane/IPA + CH3OH/H2O + 0.01 M Ammonium 0.1% Acetic Acid Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.0 min Run Time = 11.8 min k'1 = 1.63 k'1 = 3.21 α = 1.64 α = 1.72 reference 46 reference 46 Naproxen (Normal Phase) Flurbiprofen Naproxen (Normal Phase) Flurbiprofen Column = (R,R)-Whelko-O 1 Column = (R,R)-Whelko-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (60/40) Mobile Phase: (90/10) Hexane/IPA + Hexane/IPA + 0.1% Acetic Acid 0.01 M Ammonium Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.5 min Run Time = 20.5 min k'1 = 1.40 k'1 = 5.90 α = 2.03 α = 1.76 reference 46 reference 46

Loxoprofen Naproxen Diisopropyl Amide Loxoprofen Naproxen Diisopropyl Amide Column = (R,R)-Whelko-O 1 10%EtOH/hex 25 cm x 4.6 mm 1 ml/min; 254 nm Mobile Phase: (85/15) 4.6 mm x 25 cm Whelk-O 1 Hexane/Ethanol + k'1 = 2.23 0.01 M Ammonium Acetate α = 1.53 Flow Rate = 1.5 mL/min reference 26 Detection = UV 254 nm CH3 Run Time = 15.0 min N k'1 = 5.41 α = 1.30 O reference 46 H3CO

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 9 REGIS Aryl Propionic Acid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 3,5-Dimethylanilide-R,S-Ibuprofen Naproxen Methyl Ester Column = (3R,4S)-Pirkle 1-J Naproxen Methyl Ester 25 cm x 4.6 mm 20% IPA/hex, 1g/L NH4OAc Mobile Phase = (85/15) 2 ml/min; 254 nm Hexane/IPA 4.6 mm x 25 cm Whelk-O 1 Flow Rate = 1.0 mL/min k'1 = 3.42 α = 1.42 Detection = UV 254 nm CH Run Time = 13.0 min reference 14 3 k'1 = 2.91 OCH3 α = 1.36 reference 46 O H3CO

Naproxen Methyl Amide Indoprofen Naproxen Methyl Amide Indoprofen 20% IPA/hex, 1g/L NH4OAc Column = (S,S)-Whelk-O 1 2 ml/min; 254 nm 10/100 (FEC) 25 cm x 4.6 mm 4.6 mm x 25 cm Whelk-O 1 Mobile Phase = (80/20) k'1 = 18.73 Hexane/Ethanol + α = 1.41 0.01 M Ammonium reference 14 CH3 H Acetate N Flow Rate = 2.0 mL/min CH3 Detection = UV 254 nm Run Time 17.0 min O H CO k'1 = 8.93 3 α = 1.32 reference 46 Naproxen α-Trityl-2-naphthalene Propionic Acid Naproxen α-Trityl-2-naphthalene ® Extract from Aleve tablet (99.4%ee) CH3 propionic acid

80:20:0.5 hexane/IPA/HOAc OH Column = (R,R)-ULMO 2 ml/min; 254 nm 25 cm x 4.6 mm Run Time = 10 min Mobile Phase = H3C O 4.6 mm x 25 cm (S,S) O (97/3)Hexane/IPA Whelk-O 1 Flow Rate = 1.0 mL/min Sample prep: 1/2 tablet partitioned Detection = UV 254 nm between 1M HC1 (2 ml) and Run Time = 10.0 min CH2C12 (5 ml) with sonication. k'1 = 1.57 CH2C12 layer filtered through glass α = 1.79 wool and injected reference 46

2-(4-Hydroxy-Phenoxy) Propionic Acid Rebamipide 2-(4-Hydroxy-Phenoxy) Rebamipide Propionic Acid Column = (S,S)-Whelk-O 2 Column = (R,R)-ULMO 10/100 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (85/15) Mobile Phase: (97/3) Hexane/Ethanol Hexane/Ethanol + 0.1% TFA + 0.1% TFA Flow Rate = 2.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 220 nm Detection = UV 254 nm k'1 = 9.64 Run Time = 22.5 min α = 1.21 k'1 = 9.02 reference 46 α = 1.27 reference 46

10 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Aryl Propionic Acid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) REGIS Hydratropic Acid Carprofen Hydratropic Acid Carprofen Column = (R,R)-Whelk-O 1 Column = (R,R)-Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (85/15) Mobile Phase: (98/2) Hexane/IPA Hexane/IPA + 0.1% Acetic Acid + 0.1% Acetic Acid Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm k'1 = 4.70 k'1 = 1.89 α = 1.73 α = 1.34 reference 46 reference 46

Other Carboxylic Acids REGIS Tetrahydropyrimindine Carboxylic Acid Phenylbutyric acid Column: (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (90/10) Mobile Phase = (99/1) Heptane/IPA + 0.1% TFA Heptane/IPA + 0.1% TFA Flow Rate: 1.0 mL/min Flow Rate = 2.0 mL/min Detection: UV 215 nm Detection = UV 215 nm Run Time: 14 min Run Time = 6.5 min k'1 = 3.38 k'1 = 3.19 α = 1.21 α = 1.16 reference 48 reference 48

99:1:0.1 hexane/IPA/HOAc 99:1:0.1 hexane/IPA/HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 17 min O Run Time = 16 min 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 4.06 k'1 = 3.45 α = 1.28 OH α = 1.38 O reference 18 reference 18 OH

Ph Ph Ph k'1 = 3.45 138 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 11 REGIS Other Carboxylic Acids 2-Phenylcyclopropane Carboxylate Trolox 2-Phenylcyclopropane Trolox Carboxylate 95:5:0.1 hexane/IPA/HOAc 99:1 hexane/IPA 1 ml/min; 254 nm CH 1 ml/min; 220 nm Run Time = 19 min 3 Run Time = 18 min 4.6 mm x 25 cm HO 4.6 mm x 25 cm Whelk-O 1 O Whelk-O 1 k' = 4.19 k' = 5.09 CH 1 1 H C O 3 α = 1.34 OH α = 1.21 3 OH reference 18 reference 18 CH3 O

Mandelic Acid 1,1'-binaphthyl-2,2'-diylhydrogen phosphate

Mandelic Acid 56:44 H2O/MeOH, 0.1% 0.1% HOAc in water HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 13 min Run Time = 18 min 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.08 OH k'1 = 4.46 α = 1.13 α = 1.27 OH O reference 18 O P O O OH

Trolox Calcium Channel Blocker Column = (R,R)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm CH3 25 cm x 4.6 mm Mobile Phase = (95/5) HO Mobile Phase = (99/1) Hexane/IPA + OH Heptane/IPA + 0.1% TFA 0.1% Acetic acid Flow Rate = 1.0 mL/min

Flow Rate = 1.5 mL/min H3C O Detection = UV 230 nm O Detection = UV 280 nm CH3 Run Time = 6 min CH3 Run Time = 12.5 min k'1 = 0.55 k'1 = 2.18 α = 2.06 α = 2.68 reference 48 reference 46

Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase = (95/5) Hexane/IPA + 0.1% Hexane/IPA + 0.1% Trifluoroacetic Acid Trifluoroacetic Acid Flow Rate = 2.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 8.5 min Run Time = 8.5 min k'1 = 2.03 k'1 = 4.20 α = 2.10 α = 1.11 reference 49 reference 50

12 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Other Carboxylic Acids REGIS

Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase = (95/5) Hexane/IPA + 0.1% Hexane/IPA + 0.1% Trifluoroacetic Acid Trifluoroacetic Acid Flow Rate = 2.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.0 min Run Time = 14.5 min k'1 = 2.07 k'1 = 7.24 α = 2.62 α = 1.22 reference 49 reference 50

Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (95/5) Mobile Phase = (95/5) Hexane/IPA + 0.1% Hexane/IPA + 0.1% Trifluoroacetic Acid Trifluoroacetic Acid Flow Rate = 2.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 3.5 min Run Time = 11.5 min k' = 0.84 1 k' = 5.44 α = 1.36 1 α = 1.34 reference 49 reference 50

Phenylsuccinic Acid 4-Chloromandelic Acid Phenylsuccinic Acid 4-Chloromandelic Acid Column = (S,S)-ULMO Column = (R,R)-Whelk-O 2 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase = (70/30)

Hexane/IPA + 0.1% TFA H2O/CH3OH Flow Rate = 1.0 mL/min + 0.1% Acetic Acid Detection = UV 254 nm Flow Rate = 1.0 mL/min Run Time = 8.5 min Detection = UV 254 nm k'1 = 1.71 Run Time = 10.0 min α = 1.22 k'1 = 1.95 reference 48 α = 1.43 reference 46

α-Methoxyphenyl Acetic Acid Ketorolac α-Methoxyphenyl Acetic Acid Ketorolac Column = (S,S)-Whelk-O 1 Column = (R,R)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (90/10) Mobile Phase = (98/2) Hexane/Ethanol + Hexane/IPA + 0.01 M Ammonium Acetate 0.1% TFA Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 220 nm Detection = UV 254 nm Run Time = 10.0 min Run Time = 20.0 min k'1 = 2.96 k'1 = 8.87 α = 1.61 α = 1.15 reference 46 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 13 REGIS Other Carboxylic Acids Suprofen Ditoluoyltartaric Acid Suprofen Ditoluoyltartaric Acid Column = (S,S)-Whelk-O 1 Column: (S,S)-ULMO 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (90/10) Mobile Phase = Hexane/IPA + 0.1% TFA (80/20) Hexane/IPA + Flow Rate: 1.0 mL/min 0.01 M Ammonium Acetate Detection: UV 254 nm Flow Rate = 2.0 mL/min Run Time = 12.0 min Detection = UV 254 nm k'1 = 2.47 Run Time = 18.0 min α = 1.19 k'1 = 9.76 reference 48 α = 1.27 reference 46 Trolox-methylether 1-Cyclopentyl-1-phenylacetic Acid Trolox-methylether 1-Cyclopentyl-1-phenylacetic Acid Column: (S,S)-ULMO Column: (S,S)-ULMO 25 cm 25 cm x 4.6 mm x 4.6 mm Mobile Phase: (90/10) Mobile Phase: (99/1) Hexane/IPA Hexane/IPA + 0.1% TFA + 0.1% TFA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time = 12.0 min Run Time = 6.0 min k'1 = 2.46 k'1 = 0.32 α = 1.19 α = 2.50 reference 48 reference 48

1-Cyclohexyl-1-phenylacetic Acid 2-(2-Chloro-4-methylphenoxy)propionic Acid 1-Cyclohexyl-1-phenylacetic Acid 2-(2-Chloro-4-methylphenoxy)propionic Acid Column: (S,S)-ULMO 25 cm Column: (S,S)-ULMO 25 cm x 4.6 mm x 4.6 mm Mobile Phase: (99/1) Mobile Phase: (99/1) Hexane/IPA + 0.1% TFA Hexane/IPA + 0.1% TFA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time = 11.0 min Run Time = 13.0 min k'1 = 2.22 k'1 = 2.53 α = 1.11 α = 1.18 reference 48 reference 48

Vanilmandelic Acid 2-(3-Chlorophenoxy) Propionic Acid Vanilmandelic Acid 2-(3-Chlorophenoxy) Propionic Acid Column: (S,S)-Whelk-O 1 Column: (R,R)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 10/100 (FEC) 25 cm x 4.6 Moblie Phase: (85/15) Moblie Phase: (99/1) Hexane/Ethanol + Hexane/IPA 0.01 M Ammonium Acetate Flow Rate: 1.5 mL/min Flow Rate: 2.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 17.0 min Run Time: 22.0 min k'1 = 6.09 k'1 = 12.34 α = 1.42 α = 1.27 reference 46 reference 46

14 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Other Carboxylic Acids REGIS 4-(Trifluoromethyl)mandelic Acid 2,3-Dibenzoyl-Tartaric Acid 4-(Trifluoromethyl)mandelic Acid 2,3-Dibenzoyl-Tartaric Acid Column: (S,S)-Whelk-O 1 Column: (R,R)-ULMO 25 cm x 4.6 10/100 25 cm x 4.6 mm Moblie Phase: (92/8) Mobile Phase: (90/10) Hexane/Ethanol + Hexane/Ethanol + 0.01 M Ammonium 10 mM Ammonium Acetate Acetate Flow Rate: 1.5 mL/min Flow Rate: 1.5 mL/min Detection: UV 254 nm Detection: UV 254 nm k'1 = 4.87 Run Time: 11.0 min α = 1.33 k'1 = 3.59 reference 46 α = 1.40 reference 46

Basic Nitrogen REGIS Basic Amine REGIS Troger’s Base trans-11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene Column: (R,R)-Whelk-O 1 trans-11,12-Diamino-9,10- (10/100) (FEC) 25 cm x 4.6 mm dihydro-9,10-ethanoanthracene Mobile Phase: (96/4) Hexane/Ethanol Column = ChiroSil® RCA(+) Flow Rate: 1.5 mL/min 15 cm x 4.6 mm Detection: UV 254 nm Mobile Phase = (80/20) Run Time = 10.0 min CH2OH/H2O k'1 = 2.52 + 0.1% Phosphoric acid α = 1.80 Flow Rate = 1.0 mL/min reference 46 Detection = UV 220 nm Run Time = 10.7 min k'1 = 3.22 α = 1.65 reference 46

30% EtOH/hexane 1 ml/min; 254 nm O run time = 18 min 4.6 mm x 25 cm Whelk-O 1 N Bz k'1 = 2.46 α = 2.09 reference 18 N

CH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 15 REGIS Esters, Lactones, Ketones, Anhydrides Methyl Mandelate 2-Methyl-1-Indanone Methyl Mandelate 2-Methyl-1-Indanone 73:27:0.1 H2O/CH3CN/HOAc 99:1 hexane/IPA 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 20 min Run Time = 15 min O 4.6 mm x 25 cm Whelk-O 1 OH 4.6 mm x 25 cm Whelk-O 1 k'1 = 5.27 O k'1 = 4.00 α = 1.15 α = 1.12 CH3 CH3 reference 18 reference 18 O

95:5:0.5 hexane/IPA/HOAc 95:5:0.5 hexane/IPA/HOAc 1 ml/min; 280 nm 1 ml/min; 280 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 O k'1 = 1.27 O k'1 = 2.85 α α = 1.28 O = 1.70 O reference 26 OH reference 26 OEt

CH3 CH3 H3C

93:7:0.1 hexane/IPA/HOAc O 95:5:0.5 hexane/IPA/HOAc O 1 ml/min; 254 nm 1 ml/min; 280 nm O run time = 30 min 4.6 mm x 25 cm Whelk-O 1 OEt 4.6 mm x 25 cm Whelk-O 1 O k'1 = 2.75 k'1 = 8.10 α = 2.53 CH3 α = 1.21 reference 26 reference 18 O

90:10 hexane/IPA 20% IPA/hex 1 ml/min; 254 nm 2 ml/min; 254 nm O 4.6 mm x 25 cm Whelk-O 1 O 4.6 mm x 25 cm Whelk-O 1 O k'1 = 3.41 k'1 = 5.66 α = 1.81 α = 1.29 reference 7 reference 7

H3CO

16 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Esters, Lactones, Ketones, Anhydrides REGIS 3-Methyl-1-Indanone DPHB 3-Methyl-1-Indanone DPHB k'1 = 6.11 6% EtOH/hexane α = 1.18 O 1 ml/min; 254 nm 99:1 hexane/IPA Run Time = 41 min

1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 O Run Time = 20 min reference 29 4.6 mm x 25 cm Whelk-O 1 reference 18 CH3 OH

20% IPA/hex 98:2 hexane/IPA 2 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 O 4.6 mm x 25 cm Whelk-O 1 k'1 = 1.17 k'1 = 7.82 O α = 1.66 α = 1.12 reference 7 reference 7 H C 3 S

EtO MeOH/IPA/hexane Column = L-Leucine 1 ml/min; 254 nm O 25 cm x 4.6 mm Run Time = 17 min Mobile Phase = (99.5/0.5) 4.6 mm x 25 cm Whelk-O 1 Hexane/IPA k'1 = 12.73 H Flow Rate = 1.0 mL/min α = 1.16 O Detection = UV 254 nm O O reference 19 O Run Time = 11.5 min H k'1 = 2.42 α = 1.21 reference 57 O OEt

97:3 hexane/IPA 10% IPA/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 27 min 4.6 mm x 25 cm O 4.6 mm x 25 cm Whelk-O 1 O Whelk-O 1 k'1 = 8.46 k'1 = 2.27 α α = 1.08 OCH3 = 1.11 reference 18 reference 26 O O

H3CO

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 17 REGIS Esters, Lactones, Ketones, Anhydrides 2-Methyl-1-Tetralone Diperodon 2-Methyl-1-Tetralone Diperodon 99:1 hexane/IPA Column = (R)-α-Burke 2 25 cm x 4.6 mm

1 ml/min; 254 nm Mobile Phase = (48/48/4) CH2Cl2/Hexane/Ethanol Run Time = 12 min O + 1.5 mM Ammonium Acetate 4.6 mm x 25 cm Whelk-O 1 Flow Rate = 1.0 mL/min k'1 = 2.76 CH3 Detection = UV 254 nm α = 1.11 Run Time = 9.0 min reference 18 k'1 = 1.7 α = 1.25 reference 46

1,3,5-Triphenylpent-4-yn-1-one 1,3,5-Triphenylpent-4-yn-1-one 10% IPA/hexane Column = (S,S)-ULMO 1 ml/min; 254 nm 25 cm x 4.6 mm 4.6 mm x 25 cm Mobile Phase = Whelk-O 1 Hexane + k'1 = 0.67 0.5% IPA α = 1.16 Flow Rate = 1.0 mL/min reference 26 O O Detection = UV 254 nm Run Time = 6.5 min k'1 = 1.19 α = 1.19 reference 46

Column = (S,S)- Column = (S,S)- Whelk-O 1 Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase = (98/2) (98/2) Hexane/IPA Hexane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = Run Time = 34.0 min UV 254 nm k'1 = 8.00 Run Time = 20.5 min α = 1.44 k'1 = 1.62 reference 51 α = 4.18 reference 51

Column = (S,S)-β-Gem 1 Column = D-Phenylglycine 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (99.5/0.5) Mobile Phase = 99/1) Hexane/IPA Hexane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 14.5 min Run Time = 13.5 min k'1 = 2.67 k'1 = 3.10 α = 1.43 α = 1.18 reference 57 reference 57

18 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Esters, Lactones, Ketones, Anhydrides REGIS Buckminsterfullerene-Enone [2+2] Photoadducts Semi-prep separation on analytical column 2:1 toluene/hexane 1 ml/min; 400 nm Run Time = 22 min Sample: 100µ1 of 5 mg/ml solution (0.5 mg) 4.6 mm x 25 cm Whelk-O 1 reference 8

Ethyl-2-(p-Hydroxyphenoxy) Propionate Tert-butyl-2-(benzamido) cyclopentyl carbamate Ethyl-2-(p-Hydroxyphenoxy) Tert-butyl-2-(benzamido) Propionate cyclopentyl carbamate Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98/2) Mobile Phase = (95/5) Hexane/Ethanol Hexane/IPA Flow Rate = 2.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 21.1 min k'1 = 3.65 k'1 = 12.72 α = 1.46 α = 1.15 reference 46 reference 46 1’-Acetoxychavicol Acetate 1’-Acetoxychavicol Acetate Column = (R,R)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 mm Mobile Phase = (90/10) Hexane/IPA Flow Rate = 1.5 mL/min Detection = UV 254 nm k'1 = 5.94 α = 2.05 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 19 REGIS Amides, Imides, Carbamates, etc.

EEDQ O N EEDQ methanol O 90:10 hexane/IPA 2 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 6 min N Run Time = 25 min 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 O Whelk-O 1 NO k'1 = 1.75 k'1 = 1.53 α = 1.20 α k'1 = 1.75 = 2.13 OO reference 7 reference 18

CBZ nornicotine CBZ-Val CBZ nornicotine CBZ-Val 1:3 MeOH/dichloromethane 95:5:0.1 hexane/IPA/HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 5 min Run Time = 19 min O 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 N Whelk-O 1 OH ON k'1 = 0.37 k'1 = 5.49 α O α = 1.38 N O = 1.13 H O reference 7 reference 18

CBZ nornicotine

BOC-Ala CBZ-Phe BOC-Ala CBZ-Phe 98:2:0.2 hexane/IPA/HOAc 95:5:0.1 hexane/IPA/HOAc 1 ml/min; 220 nm 1 ml/min; 254 nm Run Time = 17 min Run Time = 40 min 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 4.43 k'1 = 10.2 O α = 1.09 O CH3 α = 1.20 OH reference 18 OH reference 18 ON ON H O H O

80:20:0.1 hexane/IPA/HOAc O 15% EtOH/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 25 min O Run Time = 16 min 4.6 mm x 25 cm H 4.6 mm x 25 cm N Ph Whelk-O 1 Whelk-O 1 k'1 = 5.97 k'1 = 3.79 α = 1.36 α = 1.66 Ph reference 18 O reference 18 N

OH

O

20 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Amides, Imides, Carbamates, etc. REGIS

ethyl acetate ethyl acetate 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 H 4.6 mm x 25 cm Whelk-O 1 CH3 k'1 = 0.50 k'1 = 0.64 α = 1.56 H α = 2.06 H reference 7 N O reference 26 N O

CH3 CH3

ethyl acetate ethyl acetate 1 ml/min; 254 nm 1 ml/min; 254 nm H 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm N O k'1 = 0.16 Whelk-O 1 α = 5.56 H k' = 0.14 1 CH reference 7 N O α = 3.21 3 reference 26 CH3 k'1 = 0.14 α = 3.21

95:5:0.5 hexane/IPA/HOAc 2%EtOH/hex 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 14.97 k'1 = 5.13 α = 1.12 α = 1.03 CH3 reference 7 reference 26 N

H NO O

Me Et

10% IPA/hexane 20% IPA/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.64 p-Ts k'1 = 4.45 p-Ts α = 1.11 N α = 1.34 N reference 26 reference 26

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 21 REGIS Amides, Imides, Carbamates, etc.

20% IPA/hexane 20% IPA/hexane 2 ml/min; 254 nm CH O 2 ml/min; 254 nm CH O Run Time = 4 min 3 Run Time = 4 min 3 (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 3.72 k'1 = 1.48 N α = 3.17 N CH3 α = 11.6 reference 38 H reference 38 H Cl

20% IPA/hexane 20% IPA/hexane 2 ml/min; 254 nm 2 ml/min; 254 nm CH3 O CH3 O Run Time = 4 min Run Time = 4 min (S,S) Whelk-O 1 (S,S) Whelk-O 1 k' = 4.10 k' = 1.61 1 N CH3 1 N α = 5.12 α = 12.8 reference 38 H reference 38 H I Br

20% IPA/hexane 20% IPA/hexane 2 ml/min; 254 nm 2 ml/min; 254 nm CH3 O Run Time = 4 min CH3 O Run Time = 4 min ( ) Whelk-O 1 ( ) Whelk-O 1 S,S S,S N k'1 = 1.39 k'1 = 1.75 α = 6.74 N α = 13.7 reference 38 reference 38 H H Br

CH3 20% IPA/hexane 20% IPA/hexane 2 ml/min; 254 nm CH O 2 ml/min; 254 nm Run Time = 4 min 3 Run Time = 4 min (S,S) Whelk-O 1 (S,S) Whelk-O 1 H k'1 = 1.17 N k'1 = 10.87 α = 7.29 α = 1.29 H3C N reference 38 H reference 38 OEt F P OEt O

22 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Amides, Imides, Carbamates, etc. REGIS

CH3 CH3 20% IPA/hexane 20% IPA/hexane 2 ml/min; 254 nm 2 ml/min; 254 nm Run Time = 4 min Run Time = 4 min (S,S) Whelk-O 1 (S,S) Whelk-O 1 H k'1 = 0.83 H k'1 = 0.84 α = 1.39 H3C N α = 1.55 H3C N reference 38 OEt reference 38 OEt P OEt P OEt O O F Cl

H CH3 20% IPA/hexane 10% acetonitrile H H H 2 ml/min; 254 nm in CO2 Run Time = 4 min (S,S) Whelk-O 1 N (S,S) Whelk-O 1 k' = 8.5 H 1 H k'1 = 0.86 α = 1.025 α = 1.66 H3C N reference 39 H O reference 38 OEt DD P OEt

O D D Br D

TMS H H H 10% acetonitrile H 10% acetonitrile Br H H in CO2 N in CO2 (S,S) Whelk-O 1 H (S,S) Whelk-O 1 N k'1 = 25 O k'1 = 19.7 H α = 1.025 H α = 1.025 reference 39 DD reference 39 H O DD D D

D D

TMS Br

Column = (S,S)-Whelk-O 1 Column = (R,R)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (90/10) Mobile Phase = (80/20) Hexane/IPA Hexane/IPA Flow Rate = 1.0 mL/min Flow Rate = 2.0 Detection = UV 254 nm mL/min Run Time = 46.0 min Detection = UV 254 k'1 = 2.70 nm α = 6.02 Run Time = 19.0 min reference 51 k'1 = 7.53 α = 1.77 reference 52

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 23 REGIS Amides, Imides, Carbamates, etc. β-Lactam Cyclopentyl Benzoyl-Diamide

β-Lactam Cyclopentyl Benzoyl-Diamide Column: (S,S)- Column: (S,S)-ULMO DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (90/10) Mobile Phase: (48/48/2) Hexane/IPA

Hex/CH2Cl2/IPA Flow Rate: 1.5 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 8.7 min Run Time: 14.0 min k’1: 2.62 α k’1: 3.40 : 1.47 α: 1.33 reference 46 reference 59

REGIS Epoxides Styrene Oxide Stilbene Oxide Styrene Oxide Stilbene Oxide 1% IPA/hexane 10% IPA/hexane 1 ml/min; 254 nm O 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 k'1 = 0.45 O k'1 = 1.37 α = 2.00 α = 1.37 reference 18 reference 18

m-Cl Styrene Oxide 0.1% HOAc in hexane m-Cl Styrene Oxide 1 ml/min; 254 nm hexane Run Time = 20 min 1 ml/min; 220 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm k'1 = 5.92 Whelk-O 1 O α = 1.12 reference 30 Cl reference 18 O

24 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Alcohols REGIS Ibuprofenol 1,2,3,4-Tetrahydro-1-Naphtol Ibuprofenol 1,2,3,4-Tetrahydro-1-Naphtol 99:1 hexane/IPA Column = (R,R)-ULMO 1 ml/min; 254 nm 25 cm x 4.6 mm OH Run Time = 14 min CH Mobile Phase = (99/1) 4.6 mm x 25 cm Whelk-O 1 3 Hexane/IPA k'1 = 3.38 OH Flow Rate = 1.0 mL/min α = 1.05 Detection = UV 254 nm reference 26 Run Time = 10.5 min k'1 = 2.17 α = 1.30 reference 46

Tert Butyl Phenyl Carbinol α-Naphthyl Methyl Carbinol Tert Butyl Phenyl Carbinol α-Naphthyl Methyl Carbinol Column = (S,S)-ULMO Column = (R,R)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (99/1) Mobile Phase = (99/1) OH Heptane/IPA Hexane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 215 nm Detection = UV 254 nm CH3 Run Time = 6.0 min Run Time = 14.5 min k'1 = 4.60 k'1 = 3.49 α = 1.46 α = 1.25 reference 46 reference 46

9-Anthryl Trifluoromethyl Carbinol Acenaphthenol 9-Anthryl Trifluoromethyl Acenaphthenol Carbinol Column: (R,R)-ULMO OH HO CF Column = (R,R)-ULMO 3 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (95/5) Mobile Phase = (95/5) Hexane/IPA Hexane/IPA Flow Rate: 1.0 mL/min Flow Rate = 1.0 mL/min Detection: UV 254 nm Detection = UV 254 nm Run Time: 10 min Run Time = 10 min k’1: 1.68 k'1 = 1.36 α: 1.46 α = 2.02 reference 46 reference 46

2% IPA/hexane 80:20 hexane/IPA 1 ml/min; 220 nm 1 ml/min; 254 nm 4.6 mm x 25 cm run time = 10 min Whelk-O 1 OH 4.6 mm x 25 cm H3C OH k'1 = 1.76 Whelk-O 1 α = 1.13 k'1 = 1.22 reference 18 α = 2.08 reference 26

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 25 REGIS Alcohols Beta Naphthyl Methyl Carbinol 1,1’-Bi-2-Naphthol Beta Naphthyl Methyl Carbinol 1,1’-Bi-2-Naphthol Column: (R,R)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (97/3) Hexane/IPA OH Mobile Phase = (98/2) Flow Rate: 1.0 mL/min Hexane/IPA + 0.1% TFA Detection: UV 254 nm Flow Rate = 1.0 mL/min Run Time: 9 min CH3 Detection = UV 254 nm k’1: 1.64 Run Time = 18.0 min α: 1.34 k'1 = 4.84 reference 46 α = 1.24 reference 48

Tetrahydrobenzopyrene-7-ol 9-Anthrylethanol Tetrahydrobenzopyrene-7-ol 9-Anthrylethanol 80:20 hexane/IPA Column = (S,S)-ULMO 1 ml/min; 254 nm OH 25 cm x 4.6 mm run time = 22 min Mobile Phase = (95/5) Heptane/IPA 4.6 mm x 25 cm Flow Rate = 1.0 mL/min Whelk-O 1 Detection = UV 215 nm k'1 = 6.10 Run Time = 12 min α = 1.18 k'1 = 1.82 reference 18 α = 1.74 reference 48

1-Naphthyl-2-butanol 2-Naphthyl-2-butanol 1-Naphthyl-2-butanol 2-Naphthyl-2-butanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase = (95/5) Heptane/IPA Heptane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 215 nm Detection = UV 215 nm Run Time = 6 min Run Time = 8 min k'1 = 0.80 k'1 = 1.00 α = 1.35 α = 1.93 reference 48 reference 48

1% IPA/hexane Column = (S,S)-Whelk-O 1 1 ml/min; 254 nm 25 cm x 4.6 mm 4.6 mm x 25 cm Whelk-O 1 Mobile Phase = (99/1) k'1 = 3.38 Hexane/IPA α = 1.05 CH3 Flow Rate = 1.0 mL/min reference 7 Detection = UV 254 nm OH Run Time = 18.5 min k'1 = 5.59 α = 1.09 reference 55

26 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Alcohols REGIS 1-Phenylpentanol Phenyl Tribromomethyl Carbinol 1-Phenylpentanol Phenyl Tribromomethyl Carbinol Column = (S,S)-ULMO Column = (R,R)-ULMO OH 25 cm x 4.6 mm 25 cm x 4.6 mm

Mobile Phase = (99/1) Mobile Phase = (99/1) CBr n-Heptane/1,2- Hexane/IPA 3 Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 9 min Run Time = 7.0 min k'1 = 1.87 k'1 = 1.65 α = 1.25 α = 1.45 reference 46 reference 60

Phenyl Methyl Carbinol Phenyl Ethyl Carbinol Phenyl Methyl Carbinol Phenyl Ethyl Carbinol Column = (R,R)-ULMO Column = (R,R)-ULMO 25 cm x 4.6 mm OH 25 cm x 4.6 mm OH Mobile Phase = 100% Mobile Phase = (99/1) Hexane Hexane/IPA

Flow Rate = 1.0 mL/min CH3 Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 14 min Run Time = 6.5 min k'1 = 3.11 k'1 = 1.06 α = 1.30 α = 1.30 reference 46 reference 46

Phenyl Propyl Carbinol 1,1,2,-Triphenyl-1,2-Ethanediol Phenyl Propyl Carbinol 1,1,2,-Triphenyl-1,2-Ethanediol Column = (R,R)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = 100% Hexane OH Mobile Phase = (99/1) Flow Rate = 1.0 mL/min Heptane/IPA Detection = UV 254 nm Flow Rate = 1.0 mL/min Run Time = 12 min Detection = UV 215 nm k'1 = 2.25 Run Time = 13 min α = 1.56 k'1 = 2.59 reference 46 α = 1.14 reference 48

Column = (S,S)-Whelk-O 1 Column = (R,R)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm OH Mobile Phase = (80/20) Mobile Phase = (99/1) Hexane/IPA Hexane/IPA Flow Rate = 2.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 24.0 min Run Time = 10 min k'1 = 13.30 k'1 = 1.97 α = 1.11 α = 1.37 reference 55 reference 48

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 27 REGIS Alcohols 1,1’-Binaphthol Monomethylether Terfenadine 1,1'-Binaphthol Terfenadine Monomethylether Column = (R,R)-Whelk-O 1 Column: (S,S)-ULMO 25 cm 25 cm x 4.6 mm x 4.6 mm Mobile Phase = (97/3) Mobile Phase: (98/2) Hexane/Ethanol + Hexane/IPA + 0.1% TFA 0.01 M Ammonium Flow Rate: 1.0 mL/min Acetate Detection: UV 254 nm Flow Rate = 1.5 mL/min Run Time = 11.0 min Detection = UV 254 nm k'1 = 2.23 Run Time = 15.0 min α = 1.28 k'1 = 5.91 reference 48 α = 1.20 reference 46 Propafenone Trans Phenyl Cyclohexanol Analytical vs. Preparative Run Propafenone Trans Phenyl Cyclohexanol Column = (R,R)-Whelk-O 1 Analytical vs. Preparative Run 25 cm x 4.6 mm Column = (S,S)-ULMO Mobile Phase = (47/47/6) 25 cm x 4.6 mm CH2Cl2/Hexane/ Mobile Phase = (99/1) Ethanol + 0.01 M Heptane/IPA Ammonium Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 270 nm Detection = UV 254 nm Run Time = 7.0 min 2.8 MG Run Time = 11.0 min reference 48 k'1 = 3.99 1.4 MG α = 1.25 0.14 MG reference 46 2-Methoxyphenyl Phenyl Carbinol Phenyl cyclohexyl carbinol 2-Methoxyphenyl Phenyl Carbinol Phenyl cyclohexyl carbinol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (99/1) Mobile Phase: (99/1) Heptane/IPA Heptane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 215 nm Detection = UV 215 nm Run Time = 12.0 min Run Time = 6.5 min k'1 = 2.92 k'1 = 0.97 α = 1.13 α = 1.39 reference 48 reference 48

Phenyl isopropyl carbinol Phenyl phenylethyl carbinol Phenyl isopropyl carbinol Phenyl phenylethyl carbinol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (99/1) Mobile Phase = (99/1) Heptane/IPA Heptane/IPA Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 215 nm Detection = UV 215 nm Run Time: 6 min Run Time = 9.5 min k'1 = 0.86 k'1 = 1.81 α = 1.38 α = 1.30 reference 48 reference 48

28 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Alcohols REGIS Methyl 3-phenyl-3azido-2hydroxypropanoate 1-(4-Methoxyphenyl)-2-butanol (Erythro-diastereomer) 1-(4-Methoxyphenyl)-2-butanol Methyl 3-phenyl-3azido-2hydroxypropanoate Column = (S,S)-ULMO (Erythro-diastereomer) 25 cm x 4.6 mm Column = (S,S)-ULMO 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (97/3) n-Heptane/1,2- Heptane/Glyme Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 215 nm Detection = UV 254 nm Run Tim = 10.5 min Run Time = 12.0 min k' = 2.34 k'1 = 2.04 1 α α = 1.16 = 1.49 reference 48 reference 60 1-(4-Methoxyphenyl)-2-propanol 1-Phenyl-2-propanol 1-(4-Methoxyphenyl)-2-propanol 1-Phenyl-2-propanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 17.5 min Run Time = 6.5 min k'1 = 5.33 k'1 = 1.72 α = 1.28 α = 1.19 reference 60 reference 60

2-Thiopheneethanol 3-Thiopheneethanol 2-Thiopheneethanol 3-Thiopheneethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.5 min Run Time = 11.5 min k'1 = 2.21 k'1 = 2.42 α = 1.12 α = 1.13 reference 60 reference 60

1-(4-Hydroxyphenyl) Ethanol 1-(o-Methoxyphenyl) Ethanol 1-(4-Hydroxyphenyl) Ethanol 1-(o-Methoxyphenyl) Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase = (98.5/1.5) n-Heptane/IPA + 0.1% TFA n-Heptane/1,2- Flow Rate = 1.0 mL/min Dimethoxyethane Detection = UV 254 nm Flow Rate = 1.5 mL/min Run Time = 8.5 min Detection = UV 254 nm k'1 = 1.491 Run Time = 11.0 min α = 1.16 k'1 = 3.27 reference 60 α = 1.29 reference 60

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 29 REGIS Alcohols 1-[(4-Phenyl) phenyl] Ethanol 1-(4-Benzyloxy) phenyl Ethanol 1-[(4-Phenyl) phenyl] Ethanol 1-(4-Benzyloxy) phenyl Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 2.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 8.5 min Run Time = 11.0 min k'1 = 3.76 k'1 = 5.21 α = 1.21 α = 1.21 reference 60 reference 60

1-(p-Bromophenyl) Ethanol 1-(p-Flurorophenyl) Ethanol 1-(p-Bromophenyl) Ethanol 1-(p-Flurorophenyl) Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 11.5 min Run Time = 10.5 min k'1 = 2.39 k'1 = 2.13 α = 1.17 α = 1.16 reference 60 reference 60

1-(m-Trifluoromethylphenyl) Ethanol 1-(p-Methylphenyl) Ethanol 1-(m-Trifluoromethylphenyl) Ethanol 1-(p-Methylphenyl) Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 9.0 min Run Time = 10.5 min k'1 = 1.66 k'1 = 2.06 α = 1.14 α = 1.21 reference 60 reference 60

1-(m-Methylphenyl) Ethanol 1-(o-Methylphenyl) Ethanol 1-(m-Methylphenyl) Ethanol 1-(o-Methylphenyl) Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.5 min Run Time = 10.5 min k'1 = 1.94 k'1 = 1.88 α = 1.26 α = 1.29 reference 60 reference 60

30 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Alcohols REGIS 1-(o-Chlorophenyl) Ethanol 1-(p-Chlorophenyl) Ethanol 1-(o-Chlorophenyl) Ethanol 1-(p-Chlorophenyl) Ethanol Column = (S,S)-ULMO Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (98.5/1.5) n-Heptane/1,2- n-Heptane/1,2- Dimethoxyethane Dimethoxyethane Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 8.5 min Run Time = 10.5 min k'1 = 1.58 k'1 = 2.18 α = 1.12 α = 1.15 reference 60 reference 60

1-(m-Chlorophenyl) Ethanol Phenylethylene Glycol 1-(m-Chlorophenyl) Ethanol Phenylethylene Glycol Column = (S,S)-ULMO Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) 25 cm x 4.6 mm Mobile Phase = (98.5/1.5) Mobile Phase = (99/1) n-Heptane/1,2- Hexane/Ethanol Dimethoxyethane Flow Rate = 2.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 18.7 min Run Time = 10.5 min k'1 = 11.62 α k'1 = 2.13 = 1.11 α = 1.17 reference 46 reference 60

Ranolazine Ranolazine Column = (R,R)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 mm Mobile Phase = (65/35) Hexane/IPA + 35 mM Ammonium Acetate Flow Rate = 2.0 mL/min Detection = UV 220 nm k'1 = 11.51 α = 1.23 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 31 REGIS Diols, Hydroxyketones, etc. Hydrobenzoin Benzoin Hydrobenzoin Benzoin 95:5 hexane/IPA 80:20:0.5 hexane/IPA/HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 18 min 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k' = 0.86 1 O k'1 = 1.14 OH α = 1.97 α = 1.40 reference 7 reference 18 OH OH

Anisoin 98:2:0.5 hexane/EtOH/HOAc Anisoin OCH3 1 ml/min; 240 nm 80:20:0.5 O 4.6 mm x 25 cm Whelk-O 1 hexane/IPA/HOAc k'1 = 4.20 1 ml/min; 254 nm α = 1.28 OH 4.6 mm x 25 cm OH reference 26 Whelk-O 1 H3CO k'1 = 3.07 α = 2.34 OH reference 26

Ipsdienol Ipsdienol 60:40 hexane/EtOH 2% IPA/hexane 1 ml/min; 240 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 Run Time = 8 min k'1 = 2.03 OCH3 4.6 mm x 25 cm α = 1.32 OH Whelk-O 1 reference 26 k'1 = 0.95 HO α = 1.21 reference 18 OH H3CO

98:2:0.5 hexane/IPA/HOAc 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 k'1 = 7.54 OH α = 1.08 reference 7 OH

32 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Sulfoxides REGIS

7:2:1 hexane/IPA/CH2C12 7:2:1 hexane/IPA/CH2C12 2 ml/min; 254 nm 1 ml/min; 254 nm O Run Time = 9 min H C 4.6 mm x 25 cm 4.6 mm x 25 cm 3 O O Whelk-O 1 S Whelk-O 1 k'1 = 3.83 α CH3 k'1 = 4.10 S = 1.24 α = 1.13 CH3 reference 7 reference 18

7:2:1 hexane/IPA/CH2C12 7:2:1 hexane/IPA/CH2C12 2 ml/min; 254 nm 2 ml/min; 254 nm Run Time = 8 min Run Time = 8 min 4.6 mm x 25 cm Whelk-O 1 O 4.6 mm x 25 cm O k'1 = 3.75 Whelk-O 1 α = 1.13 S k'1 = 3.75 S reference 18 CH3 α = 1.13 CH3 reference 18 Br Br

7:2:1 hexane/IPA/CH2C12 80:20 hexane/IPA 2 ml/min; 254 nm 1.5 ml/min; 254 nm Run Time = 6 min Run Time = 14 min 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 O k' = 2.11 1 O k'1 = 1.90 α = 1.70 α S = 1.46 CH reference 31 S reference 18 3 CH3

H3C

7:2:1 hexane/IPA/CH2C12 7:2:1 hexane/IPA/CH2C12 1 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 Run Time = 11 min k'1 = 3.29 4.6 mm x 25 cm α = 2.14 Whelk-O 1 O reference 7 S S O k'1 = 5.04 α = 1.12 S reference 18 CH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 33 REGIS Sulfoxides

7:2:1 hexane/IPA/CH2C12 7:2:1 hexane/IPA/CH2C12 O 2 ml/min; 254 nm 2 ml/min; 254 nm run time = 11 min O run time = 6 min S 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 S Whelk-O 1 k'1 = 5.02 CH3 k'1 = 10.72 α = 1.21 α = 1.19 reference 18 reference 18 O k'1 = 10.72

Column: (S,S)-DACH-DNB Column: (S,S)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (27.5/27.5/45) Mobile Phase: (98/2)

CH2Cl2/Dioxane/Hex CH2Cl2/IPA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 35.0 min Run Time: 13.0 min

k’1: 10.30 k’1: 3.08 α: 1.15 α: 1.26 reference 59 reference 59

Column: (S,S)-DACH-DNB Column: (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: Mobile Phase: (98/2) (98/2)

CH2Cl2/IPA CH2Cl2/IPA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 17.0 min Run Time: 16.0 min

k’1: 3.33 k’1: 2.34 α: 1.63 α: 2.07 reference 59 reference 59

Sulfinpyrazone Omeprazole Sulfinpyrazone Omeprazole Column = (R,R)-Whelk-O 1 25 cm x 4.6 mm Column = (S)-α-Burke 2 25 cm x 4.6 mm

Mobile Phase = (75/25) Hexane/Ethanol Mobile Phase = (95/5) CH2Cl2/CH3OH + 15 mM Ammonium Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 302 nm Detection = UV 254 nm Run Time = 8.0 min Run Time = 11.0 min k'1 = 0.64 k'1 = 3.74 α = 3.04 α = 1.35 reference 46 reference 46

34 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Sulfoxides REGIS

Column: (S,S)-DACH-DNB Column: (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (40/40/20) Mobile Phase: (27.5/27.5/45)

CH2Cl2/Dioxane/Hex CH2Cl2/Dioxane/Hex Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 27.0 min Run Time: 18.0 min k’1: 7.51 k’1: 4.77 α: 1.21 α: 1.18 reference 59 reference 59

Column: Column: (R,R)-DACH-DNB (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: Mobile Phase: (95/5)

(27.5/27.5/45) CH2Cl2/IPA CH2Cl2/Dioxane/Hex Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 15.0 min

Run Time: 20.0 min k’1: 2.15 α k’1: 5.16 : 2.05 α: 1.26 reference 59 reference 59

Pantoprazole Pantoprazole Column = (R)-α-Burke 2 25 cm x 4.6 mm Mobile Phase = (48/48/4)

CH2Cl2/Hexane/Ethanol + 4 mM Ammonium Acetate Flow Rate = 1.5 mL/min Detection = UV 280 nm Run Time = 12.0 min k'1 = 4.07 α = 1.38 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 35 REGIS Phosphorous Compounds

5% 2-propanol in hexane 5% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm F3CO (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 2.26 H k'1 = 4.72 α = 1.50 N α = 1.26 H reference 40 OEt reference 40 N OEt P OEt P OEt O H3CO O

5% 2-propanol in hexane 5% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm OCF3 (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 4.26 H k'1 = 4.10 H α = 1.26 N α = 2.08 N reference 40 OEt reference 40 OEt P OEt P OEt O O

5% 2-propanol in hexane 5% 2-propanol in hexane OCF3 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 H H k'1 = 4.09 N k'1 = 6.05 α = 1.31 α = 1.63 N reference 40 OEt reference 40 OEt P OEt P OEt O O F F

5% 2-propanol in hexane 5% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 H k'1 = 9.61 k'1 = 4.58 N α = 1.75 α = 1.23 reference 40 H reference 40 OEt N P OEt OEt O P OEt O

36 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Phosphorous Compounds REGIS

5% 2-propanol in hexane 5% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 ( ) Whelk-O 1 S,S H k'1 = 7.35 k'1 = 5.87 N α = 2.54 α = 5.12 H OEt reference 40 N reference 40 OEt P OEt P OEt O O

5% 2-propanol in hexane 5:4:1 hexane/CH2C12/CH3CN 2 ml/min; 254 nm 1 ml/min; 254 nm (S,S) Whelk-O 1 4.6 mm x 25 cm k'1 = 12.30 H Whelk-O 1 α = 2.00 N k'1 = 1.11 reference 40 OEt α = 1.15 reference 7 P OEt O N

Cyclophosphamide Tertiary Phosphine Oxide Cyclophosphamide Tertiary Phosphine Oxide Column = (S,S)-Whelk-O 1 Column: (R,R)-DACH-DNB 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase: Hexane/Ethanol (37.5/37.5/25) Flow Rate = 1.5 mL/min Hex/Dioxane/IPA Detection = UV 195 nm Flow Rate: 1.0 mL/min Run Time = 16.0 min Detection: UV 254 nm k'1 = 6.31 Run Time: 14.0 min α = 1.27 k'1: 2.19 reference 46 α: 1.48 reference 59

Phosphine Selenium Oxide Secondary Phosphine Oxide Phosphine Selenium Oxide Secondary Phosphine Oxide Column: (S,S)-DACH-DNB Column: (S,S)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (75/25) CH2Cl2/IPA Mobile Phase: (70/30) Flow Rate: 1.0 mL/min Hex/CH2Cl2 Detection: UV 254 nm Flow Rate: 1.0 mL/min Run Time: 19.0 min Detection: UV 254 nm k'1: 1.49 Run Time: 13.0 min α: 4.11 k'1: 2.49 reference 59 α: 1.48 reference 59

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 37 REGIS Phosphorous Compounds Secondary Phosphine Oxide Tertiary Phosphine Oxide Secondary Phosphine Oxide Tertiary Phosphine Oxide Column: (S,S)-DACH-DNB Column: (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (90/10) Mobile Phase: CH2Cl2/IPA (42.5/42.5/15) Flow Rate: 1.0 mL/min Hex/Dioxane/IPA Detection: UV 254 nm Flow Rate: 1.0 mL/min Run Time: 8.0 min Detection: UV 254 nm k'1: 1.23 Run Time: 28.0 min α: 1.81 k'1: 8.11 reference 59 α: 1.17 reference 59

Secondary Phosphine Oxide Tertiary Phosphine Oxide Secondary Phosphine Oxide Tertiary Phosphine Oxide Column: (S,S)-DACH-DNB Column: 25 cm x 4.6 mm (R,R)-DACH-DNB Mobile Phase: 25 cm x 4.6 mm (90/10) Mobile Phase: (40/40/20) CH2Cl2/IPA Hex/Dioxane/IPA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 14.5 min Run Time: 14.0 min k'1: 2.20 k’1: 4.19 α: 1.97 α: 1.25 reference 59 reference 59

10% IPA/hex 10% EtOH/hexane 2 ml/min; 254 nm EtO 1 ml/min; 254 nm O O 4.6 mm x 25 cm Whelk-O 1 EtO P run time = 13 min k'1 = 1.35 4.6 mm x 25 cm α = 3.53 Whelk-O 1 P OCH3 reference 7 k'1 = 3.07 N OCH3 α = 1.17 H reference 18 OH N

O 10% EtOH/hexane 1 ml/min; 254 nm P OCH3 run time = 18 min 4.6 mm x 25 cm OCH3 Whelk-O 1 OH k'1 = 3.75 α = 1.38 reference 18

38 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Atropisomers REGIS

EtOAc 10% IPA/hexane 1 ml/min; 254 nm Et 1 ml/min; 254 nm 4.6 mm x 25 cm ON 4.6 mm x 25 cm Whelk-O 1 Et Whelk-O 1 O k'1 = 0.46 k'1 = 2.26 α = 2.17 CH3 α = 1.11 O reference 7 reference 7

30% IPA/hexane 30% IPA/hexane 1 ml/min; 254 nm O 1 ml/min; 254 nm S 4.6 mm x 25 cm Whelk-O 1 S 4.6 mm x 25 cm Whelk-O 1 S k'1 = 1.73 k'1 = 1.91 α = 1.64 N α = 2.13 N reference 7 reference 7 CH CH3 3 CH3

CH3

80:20:0.1% hexane/IPA/HOAc 80:20:0.1% hexane/IPA/HOAc 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O-1 ON k'1 = 3.29 k'1 = 3.23 ON α = 2.46 α = 2.66 reference 10 reference 10 CH3 CH3

80:20:0.1% hexane/IPA/HOAc 80:20:0.1% 2 ml/min; 254 nm hexane/IPA/HOAc 4.6 mm x 25 cm Whelk-O-1 2 ml/min; 254 nm k'1 = 6.24 ON 4.6 mm x 25 cm Whelk-O-1 ON α = 2.63 k'1 = 4.46 reference 10 CH α = 2.08 3 reference 10 CH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 39 REGIS Atropisomers

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm O 2 ml/min; 254 nm O (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 10.06 O k'1 = 13.00 O α = 2.37 N α = 2.57 N reference 41 reference 41

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm O 2 ml/min; 254 nm O (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 14.18 O k'1 = 12.41 O α = 2.78 N α = 2.74 N reference 41 reference 41

20% 2-propanol in hexane 20% 2-propanol in hexane O 2 ml/min; 254 nm O 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 16.29 O k'1 = 15.59 O α = 3.15 N α = 3.74 N reference 41 reference 41

20% 2-propanol in hexane O 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm O (S,S) Whelk-O 1 O (S,S) Whelk-O 1 N k'1 = 4.06 k'1 = 6.29 α α O = 2.22 = 2.25 N reference 41 reference 41

Cl

Cl

40 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Atropisomers REGIS

80:20:0.1% hexane/IPA/HOAc mixture of stereoisomers 2 ml/min; 254 nm 80:20:0.1% hexane/IPA/HOAc CH3 4.6 mm x 25 cm Whelk-O 1 O 2 ml/min; 254 nm k'1 = 7.95 ON 4.6 mm x 25 cm Whelk-O 1 ON α = 2.43 reference 10 reference 10 CH CH3 3

80:20:0.1% hexane/IPA/HOAc 80:20:0.1% hexane/IPA/HOAc 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 2.05 (S)(-) retained on (S,S) CSP α = 3.00 ON k'1 = 1.71 reference 10 α = 3.09 reference 10 ON CH3 CH3

sulfoxide atropisomer 80:20:0.1% hexane/IPA/HOAc sulfoxide atropisomer 2 ml/min; 254 nm Z diastereomer 4.6 mm x 25 cm Whelk-O 1 2% MeOH in CH2Cl2 o O k'1 = 5.11 ON 2 ml/min; 300 nm, -40 C S α = 2.04 4.6 mm x 25 cm Whelk-O 1 reference 10 CH k'1 = 1.32 CH3 3 α = 4.06 reference 21

sulfone atropisomer sulfone atropisomer sulfone atropisomer sulfone atropisomer 2% MeOH in CH2Cl2 -80°C 2 ml/min; 300 nm, -80°C O reference 22 O 4.6 mm x 25 cm Whelk-O 1 SO S k'1 = 0.54 CH α 3 = 5.79 CH3 reference 21 H3C S O

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 41 REGIS Atropisomers

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm O 2 ml/min; 254 nm O (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 3.06 k'1 = 3.00 α = 2.48 S α = 3.43 S reference 41 N reference 41 HO N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm O (S,S) Whelk-O 1 O (S,S) Whelk-O 1 k'1 = 3.25 k'1 = 2.06 S α α N = 3.20 S = 4.34 reference 41 Br N reference 41

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm O (S,S) Whelk-O 1 Cl O (S,S) Whelk-O 1 k'1 = 1.94 k'1 = 5.65 S α = 1.12 S α = 3.63 MeO N reference 41 N reference 41

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 O k'1 = 2.41 k'1 = 2.78 α = 1.80 S α = 1.90 reference 41 reference 41 S N N

42 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Atropisomers REGIS

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm O 2 ml/min; 254 nm S (S,S) Whelk-O 1 (S,S) Whelk-O CSP k'1 = 7.12 k'1 = 6.94 O α = 2.40 O α = 1.36 N reference 41 N reference 41

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm S 2 ml/min; 254 nm S (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 6.65 k'1 = 7.41 α O α O = 1.35 N = 1.48 reference 41 reference 41 N

20% 2-propanol in hexane S 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm S (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 7.12 O k'1 = 6.65 O α = 1.36 N α = 1.50 N reference 41 reference 41

20% 2-propanol in hexane S 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O O k'1 = 5.65 k'1 = 3.06 α N α = 1.64 = 2.21 S reference 41 reference 41 N

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 43 REGIS Atropisomers

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 1.94 S k'1 = 2.24 α = 1.85 α = 1.45 S reference 41 S reference 41 Cl N N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 S (S,S) Whelk-O 1 k'1 = 2.59 k'1 = 3.12 α = 1.70 S α = 2.39 S reference 41 HO N reference 41 S N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 S S k'1 = 4.12 k'1 = 3.82 α = 1.62 α = 1.62 reference 41 S reference 41 S N N

15% IPA/hexane 15% IPA/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm O2N (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 2.14 k'1 = 2.86 α = 5.56 O α = 1.86 reference 42 reference 42 N N N S N S

44 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Atropisomers REGIS

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm S (S,S) Whelk-O 1 Cl O (S,S) Whelk-O 1 k'1 = 3.12 k'1 = 2.41 α = 2.21 S α = 1.66 S reference 41 N reference 41 N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 S (S,S) Whelk-O 1 S k'1 = 1.82 k'1 = 2.41 α = 1.75 S α = 2.61 S reference 41 N reference 41 HO N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 S (S,S) Whelk-O 1 S k'1 = 2.24 k'1 = 1.53 α = 2.02 S α = 1.84 S reference 41 Br N reference 41 HO N

20% 2-propanol in hexane 20% 2-propanol in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 S (S,S) Whelk-O 1 S k'1 = 2.18 k'1 = 2.29 α α = 1.46 S = 1.80 S reference 41 N reference 41 N

Cl

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 45 REGIS Atropisomers Amlodipine Vapol Amlodipine Vapol Column = (R,R)- Column = (R,R)-ULMO Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase = (46/46/8) 100% Methanol Ph OH CH2Cl2/Hexane/Ethanol + Flow Rate = 1.5 mL/min

0.01 M Ammonium Acetate Detection = UV 254 nm Ph OH Flow Rate = 1.5 mL/min Run Time = 13 min Detection = UV 254 nm k'1 = 1.74 Run Time = 13.0 min α = 3.37 k'1 = 5.13 reference 48 α = 1.22 reference 46 Nimodipine Adam’s Acid Diethylamide Nimodipine Adam’s Acid Diethylamide Column = (R,R)-Whelk-O 1 Column = (3R,4S)-Pirkle 1-J 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase = (70/30) (65/35) Hexane/IPA

Methanol/H2O Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 17.0 min Run Time = 31.0 min k'1 = 4.11 k'1 = 9.25 α = 1.27 α = 1.13 reference 46 reference 46

15% IPA/hexane F 20% 2-propanol in hexane 1 ml/min; 254 nm O 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 11.8 k'1 = 4.00 α = 1.58 N α = 2.25 S O reference 42 N reference 41 N N S O N

NH2

46 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Optical Switches, Liquid Crystal Components, etc. REGIS Phototrigger 1 Phototrigger 2 Phototrigger 1 O Phototrigger 2 O 8% IPA in hexane 8% IPA in hexane 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 reference 24 reference 24 HH H3CCH3

Phototrigger 4 Mesogens Phototrigger 4 O Mesogens 40% IPA in hexane Schuster's candidate O 1 ml/min; 254 nm photoresolvable CN 4.6 mm x 25 cm Whelk-O 1 mesogensepoxide O reference 24 H3CCH3 derivatives reference 13 H O

H3C N O

O CN

O

H3C Phototrigger 3 Phototrigger 3 40% IPA in hexane 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 reference 24

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 47 REGIS Allenes

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid Cl 2-propanol, acetic acid F 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 0.74 O k'1 = 0.72 α = 2.38 O α = 2.33 O reference 42 reference 42 • •

H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O2N (S,S) Whelk-O 1 O k'1 = 2.20 k'1 = 0.87 α = 1.59 α = 2.90 O reference 42 O reference 42 • O H CH3 •

H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 O k'1 = 0.69 O k'1 = 0.43 O α = 3.70 α = 3.23 reference 42 • reference 42 •

H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 k'1 = 1.99 k'1 = 1.95 O α = 7.49 OH α = 4.19 reference 42 • reference 42 OH • H CH3 H CH3

48 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Allenes REGIS

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 k'1 = 1.84 O k'1 = 1.84 α = 5.68 α = 3.46 O reference 42 • reference 42 O H CH3 •

H CH3

95:5:1 hexane 95:5:1 hexane H CH 2-propanol, acetic acid 3 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 1.33 k'1 = 0.79 O α = 3.13 α = 3.23 reference 42 reference 42 • O H CH O 3 •

H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm O (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 0.93 O k'1 = 1.64 α = 3.85 α = 3.29 O reference 42 O reference 42 O • • H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid I 2-propanol, acetic acid Br 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 0.85 k'1 = 0.79 O α = 2.48 O α = 2.41 reference 42 O reference 42 O • •

H CH3 H CH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 49 REGIS Allenes

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid O2N 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 2.94 O k'1 = 7.96 O CH3 α α = 1.74 = 1.03 N reference 42 OH reference 42 • • CH3 H CH H CH3 3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 10.07 O CH3 k'1 = 5.00 α = 1.45 N α = 1.14 N reference 42 reference 42 • H •

H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 O k'1 = 7.10 k'1 = 4.47 α = 1.44 N α = 0.09 N reference 42 • H reference 42 •

H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 O k'1 = 2.76 k'1 = 4.14 α = 1.13 N α = 1.08 N reference 42 • reference 42 •

H CH3 H CH3

50 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Allenes REGIS

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 1.53 k'1 = 0.90 α = 3.56 α = 3.92 OH O reference 42 reference 42 • OH H CH • 3

H CH3

95:5:1 hexane 95:5:1 hexane H3CO 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O O k'1 = 1.04 k'1 = 1.88 α = 4.28 OH α = 3.62 OH reference 42 reference 42 • • H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid I 2-propanol, acetic acid Br 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 k'1 = 1.07 O k'1 = 1.01 O α = 2.84 α = 2.67 reference 42 OH reference 42 OH • •

H CH3 H CH3

k'1 = 0.92 k'1 = 0.90 α = 2.67 α Cl = 2.57 F 95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm O (S,S) Whelk-O 1 O (S,S) Whelk-O 1 reference 42 OH reference 42 OH • •

H CH3 H CH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 51 REGIS Allenes

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 k'1 = 3.10 k'1 = 5.46 O α N α = 1.18 = 1.34 N reference 42 • reference 42 • H H CH3 H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O k'1 = 5.21 k'1 = 3.47 α α = 1.33 O = 1.14 N reference 42 reference 42 N • • H CH3 H H CH3

95:5:1 hexane 95:5:1 hexane 2-propanol, acetic acid 2-propanol, acetic acid 2 ml/min; 254 nm 2 ml/min; 254 nm (S,S) Whelk-O 1 (S,S) Whelk-O 1 O CH O k'1 = 5.30 3 k'1 = 10.30 α = 1.06 N α = 1.11 N reference 42 reference 42 • •

H CH3 H CH3

95:5:1 hexane 2-propanol, acetic acid 2 ml/min; 254 nm (S,S) Whelk-O 1 k'1 = 6.07 O α = 1.12 N reference 42 •

H CH3

52 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Organometallic Compounds REGIS

20% IPA in hexane 20% IPA in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm O 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 (OC)3Cr O k'1 = 3.82 (OC)3Cr k'1 = 5.93 α = 1.07 α = 1.18 reference 20 H3CO reference 20 H3CO

20% IPA in hexane 20% IPA in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm (OC)3Cr 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 2.25 k'1 = 6.79 α = 1.19 O α = 1.04 (OC)3Cr reference 20 reference 20 N CH3 CH3 O k'1 = 6.79

20% IPA in hexane 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 1.48 k'1 = 1.71 α α = 1.23 O = 1.75 H reference 20 (OC)3Cr reference 20 N

O

k'1 = 1.71

20% IPA in hexane 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm 2 ml/min; 254 nm (OC)3Cr 4.6 mm x 25 cm Whelk-O 1 CH3 4.6 mm x 25 cm Whelk-O 1 CH3 k'1 = 4.93 k'1 = 2.44 α = 1.62 H α = 1.75 reference 20 reference 20 H N N

OCH3 O

k'1 = 2.44

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 53 REGIS Organometallic Compounds

20% IPA in hexane (OC)3Cr 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm CH 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 3 4.6 mm x 25 cm Whelk-O 1 CH3 k'1 = 1.79 k'1 = 3.14 α = 1.99 H α = 1.86 H reference 20 N reference 20 N

O O

k'1 = 1.79 α 199

20% IPA in hexane (OC)3Cr 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 OEt k'1 = 1.14 k'1 = 1.86 α = 1.75 H α = 1.69 H reference 20 N reference 20 N

O O

k'1 = 1.14 k'1 = 1.86

20% IPA in hexane 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm (OC)3Cr 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.71 k'1 = 11.86 α = 2.50 α = 2.08 reference 20 N reference 20 N

O OCH k' = 3.71 3 1 k'1 = 11.86

20% IPA in hexane (OC)3Cr 20% IPA in hexane (OC)3Cr 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.71 k'1 = 2.29 α = 2.50 α = 2.46 reference 20 N reference 20 N

O O k'1 = 2.29

54 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Organometallic Compounds REGIS

30% CH2Cl2 in hexane 30% CH2Cl2 in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 7.57 k'1 = 4.28 O α O α = 1.07 (OC)3Cr = 1.09 (OC)3Cr reference 20 reference 20 H H

CH3 OCH3

30% CH2Cl2 in hexane 20% IPA in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.57 O k'1 = 1.77 α = 1.06 (OC)3Cr α = 1.11 (OC)3Cr reference 20 reference 20 CH3 OH

CH3 CH3

20% IPA in hexane 20% IPA in hexane 2 ml/min; 254 nm 2 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 3.22 k'1 = 4.48 α = 1.15 (OC)3Cr α = 1.08 O reference 20 reference 20 (OC)3Cr OH

OCH3

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 55 REGIS Agricultural Compounds PPO Inhibitor PPO Inhibitor PPO inhibitor Cl PPO inhibitor Cl 10% IPA in hexane 10% IPA in hexane 2 ml/min; 254 nm O 2 ml/min; 254 nm O 4.6 mm x 25 cm CF3 4.6 mm x 25 cm CF3 Whelk-O 1 N N Whelk-O 1 N N k'1 = 5.2 O2N k'1 = 7.5 O2N α α = 1.32 O Et = 1.29 O CH reference 23 reference 23 3 H H ON ON

CH3 CH3 PPO Inhibitor PPO Inhibitor PPO inhibitor PPO inhibitor Cl Cl 10% IPA in hexane 10% IPA in hexane O 2 ml/min; 254 nm O 2 ml/min; 254 nm CF 4.6 mm x 25 cm CF 4.6 mm x 25 cm 3 Whelk-O 1 3 Whelk-O 1 N N N N k'1 = 8.0 O N k'1 = 15.1 O2N α 2 α = 1.22 = 1.04 N CH reference 23 O CH3 reference 23 H 3 H H ON ON H CH3 Tetramethrin Bromacil Tetramethrin (insecticide) Bromacil (insecticide) 2% IPA/hexane 2% IPA/hexane H 1 ml/min; 254 nm 1 ml/min; 254 nm O Run Time = 22 min O Run Time = 38 min H3C N O 4.6 mm x 25 cm 4.6 mm x 25 cm N O Whelk-O 1 Whelk-O 1 N k'1 = 11.77 k'1 = 21.43 Br α = 1.12 O α = 1.07 reference 43 reference 43 O

Permethrin Mecoprop Methyl Permethrin (insecticide) Mecoprop Methyl (insecticide) 0.2% IPA/hexane O hexane 1 ml/min; 254 nm Cl 1 ml/min; 254 nm Run Time = 16 min O Run Time = 15 min CH3 O 4.6 mm x 25 cm Cl 4.6 mm x 25 cm Whelk-O 1 O Whelk-O 1 O CH O 3 k'1 = 4.83 cis; 7.46 trans k'1 = 6.92 α = 1.11 cis; 1.24 trans α = 1.15 CH3 reference 43 reference 43 Cl

56 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Agricultural Compounds REGIS Resmethrin Metalaxyl

Resmethrin Metalaxyl (herbicide) Column: (R,R)-Whelk-O 1 70:30 hexane/IPA CH 25 cm x 4.6 mm 1 ml/min; 254 nm 3 Mobile Phase: 100% Hexane Run Time = 13 min CH3 Flow Rate:1.0 mL/min 4.6 mm x 25 cm OCH3 Dection: UV 254 nm Whelk-O 1 N Run Time: 15.0 min k'1 = 6.54 α CH3 O k'1 = 6.30 = 1.13 O α = 1.19 reference 43 reference 46 OCH3

Leptophos, Phosvel Metolachlor Leptophos, Phosvel Metolachlor (herbicide) (insecticide) 2% IPA/hexane CH hexane Cl Br 1 ml/min; 254 nm 3 1 ml/min; 254 nm S Run Time = 25 min CH3 Run Time = 10 min 4.6 mm x 25 cm 4.6 mm x 25 cm P Whelk-O 1 OCH3 Whelk-O 1 O Cl reference 43 N CH k'1 = 4.11 OCH 3 α = 1.18 3 O reference 43 Cl

Sethoxydim Chrysanthemic Acid-Ethyl Ester

Sethoxydim (herbicide) Chrysanthemic acid ethyl ester 2% IPA/hexane (mixture of isomers) 1 ml/min; 254 nm hexane Run Time = 15 min O 1 ml/min; 254 nm 4.6 mm x 25 cm Run Time = 10 min Whelk-O 1 N O 4.6 mm x 24 cm k'1 = 6.77 Whelk-O 1 α = 1.26 S reference 43 O reference 43 OH Et O

Omite Mecoprop Omite (acaricide) Mecoprop (herbicide) (mixture of isomers) 99:1:0.1 HEX/IPA/HOAc hexane 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 15 min CH3 O Run Time = 25 min 4.6 mm x 25 cm O 4.6 mm x 24 cm Whelk-O 1 O OH Whelk-O 1 k'1 = 6.54 reference 43 O O α = 1.13 CH3 S reference 43 Cl

O Omite

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 57 REGIS Agricultural Compounds Propiconazole, Tilt Devrinol, Napropamide Propiconazole, Devrinol, Napropamide Tilt (fungicide) (herbicide) 99:1:0.1 IPA/hexa- 1:1 IPA/hexane ne/HOAc 1 ml/min; 254 nm O 1 ml/min; 254 nm Run Time = 15 min Cl Run Time = 70 min O O 4.6 mm x 25 cm O 4.6 mm x 25 cm Whelk-O 1 N Whelk-O 1 k'1 = 3.17 reference 43 α = 3.00 CH3 N Cl N reference 43 N

Chlorflurecol Methlyl Crotoxyphos Chlorflurecol Methyl Crotoxyphos (herbicide) 70:30 hexane/IPA 2% IPA/hexane 1 ml/min; 254 nm 1ml/min; 254 nm Run Time = 15 min Run Time 16 min Cl 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 k'1 = 4.37 k'1 = 3.96 α = 1.93 α = 1.28 HO OCH3 reference 43 reference 43 O

Diclofop Methyl Diclofop Methyl Diclofop Methyl (herbicide) Diclofop Methyl (herbicide) 1% IPA/hexane hexane 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 30 min Run Time = 30 min 4.6 mm x 25 cm O 4.6 mm x 25 cm O Whelk-O 1 O CH Whelk-O 1 Cl 3 Cl O CH3 k'1 = 4.29 O k'1 = 14.19 O α = 1.21 α = 1.30 CH3 CH3 reference 43 O reference 43 O Cl Cl

PPO Inhibitor PPO Inhibitor PPO inhibitor PPO inhibitor 10% IPA in hexane Cl 10% IPA in hexane Cl 2 ml/min; 254 nm O 2 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm O CF Whelk-O 1 3 Whelk-O 1 CF3 k'1 = 3.9 N N k'1 = 2.4 N α O N α N = 1.11 2 = 1.12 O2N reference 23 reference 23 O CH3 O Et

O OCH3 O OEt

58 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Agricultural Compounds REGIS cis:trans Cypermethrin PPO Inhibitor cis:trans Cypermethrin PPO inhibitor Column = (3R,4S)-Pirkle 1-J 10% IPA in hexane Cl 25 cm x 4.6 mm 2 ml/min; 254 nm Mobile Phase = (98/2) 4.6 mm x 25 cm Whelk-O 1 O Hexane/IPA k'1 = 3.2 CF3 α Flow Rate = 1.0 mL/min = 1.08 N N Detection = UV 254 nm reference 23 O2N Run Time = 22.0 min k'1 (trans) = 4.59 O CH3 α (trans) = 1.19 k'1 (cis) = 6.19 α (cis) = 1.18 O OEt reference 46 PPO Inhibitor PPO Inhibitor PPO inhibitor PPO inhibitor 10% IPA in hexane Cl 10% IPA in hexane Cl 2 ml/min; 254 nm 2 ml/min; 254 nm O 4.6 mm x 25 cm Whelk-O 1 O 4.6 mm x 25 cm Whelk-O 1 CF3 k'1 = 6.1 CF3 k'1 = 4.2 α α N = 1.08 N N = 1.10 O N N reference 23 O2N reference 23 2 O CH O CH3 3 O O OO Et OO CH3

Tetramisole Silvex Methyl Ttetramisole Silvex Methyl Column = (R,R)-Whelk-O 1 (herbicide) 25 cm x 4.6 mm hexane Cl O Mobile Phase = (40/40/20) 1 ml/min; 254 nm

CH2Cl2/Hexane/Ethanol run time = 15 min O CH3 + 0.01 M Ammonium Acetate 4.6 mm x 25 cm O Flow Rate = 1.0 mL/min Whelk-O 1 CH3 Detection = UV 254 nm k'1 = 6.47 Cl Run Time = 7.0 min α = 1.05 k'1 = 0.52 reference 43 Cl α = 2.84 reference 46

Column = (R,R)- Column = (S,S)- Whelk-O 1 Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Hexane Mobile Phase = Hexane Flow Rate = 0.5 mL/min Flow Rate = 0.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 15.5 min Run Time = 18.5 min reference 54 reference 54

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 59 REGIS Agricultural Compounds Fluazifop-butyl Haloxyfop-ethoxyethyl Fluazifop-butyl Haloxyfop-ethoxyethyl Column: (S,S)-DACH-DNB Column: (S,S)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (95/5) Mobile Phase: (95/5) Hexane/IPA Hexane/IPA Temperature: 20º C Temperature: 20º C Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 11.5 min Run Time: 13.0 min k'1 = 2.65 k'1 = 3.13 α = 1.22 α = 1.25 reference: 59 reference: 59

Fenoxaprop-ethyl Quizalofop-ethyl Fenoxaprop-ethyl Quizalofop-ethyl Column: (R,R)-DACH-DNB Column: (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (95/5) Mobile Phase: (95/5) Hexane/IPA Hexane/IPA Temperature: 20º C Temperature: 20º C Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 18.0 min Run Time: 20.0 min k'1 = 4.70 k'1 = 5.22 α = 1.15 α = 1.21 reference: 59 reference: 59

Dinocap Fenvalerate Dinocap (fungicide) - mixture of isomers Fenvalerate hexane Column: (S,S)-Whelk-O 1 1 ml/min; 254 nm 10/100 (FEC) 25 cm x 4.6 mm Run Time = 15 min Mobile Phase: (99/1) 4.6 mm x 25 cm Whelk-O 1 Hexane/IPA reference 43 Flow Rate: 3.0 mL/min Detection: UV 254 nm k' = 9.36 O A1 α(A1,A2)= 2.54 k'B1= 16.79 α O2N (B1,B2)= 1.14 reference 46

NO2 O

O2NNO2

60 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS Nirvanol Mephenytoin Nirvanol Mephenytoin 20% IPA/hexane 20% IPA/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm CH Run Time = 8 min CH3H Run Time = 14 min 3H 4.6 mm x 25 cm N 4.6 mm x 25 cm N Whelk-O 1 O Whelk-O 1 O k'1 = 1.50 k'1 = 1.57 N α = 2.57 N α = 2.46 O CH reference 31 O H reference 31 3

Thalidomide Oxazepam Thalidomide Oxazepam 63:37:0.1 H2O/MeOH/HOAc Column = (R,R)-Whelk-O 1 1 ml/min; 254 nm H 25 cm x 4.6 mm Run Time = 33 min Mobile Phase = (75/25) O N O 4.6 mm x 25 cm O Hexane/IPA + 0.01 M Whelk-O 1 Ammonium Acetate k'1 = 10.19 Flow Rate = 1.5 mL/min α = 1.10 N Detection = UV 254 nm reference 18 Run Time = 9.5 min O k'1 = 2.73 α = 1.56 reference 46

Cyclothiazide Bendroflumethiazide Cyclothiazide bendroflumethiazide Column = (S,S)-ULMO k'1 = 7.89 25 cm x 4.6 mm α = 1.16 O Mobile Phase = (75/25) 1:1 hexane/IPA O O O Hexane/IPA + 0.1% 1 ml/min; 220 nm S S H H2N N Acetic Acid run time = 30 min Flow Rate = 1.5 mL/min 4.6 mm x 25 cm F3C N Detection = UV 254 nm Whelk-O 1 H Run Time = 12.0 min reference 18 k'1 = 3.71 α = 1.47 reference 46

Column: (S,S)-Whelk-O 1 Column: (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (60/40) Mobile Phase: (80/20) Ethanol/Hexane + 0.1% Hexane/IPA Triethylamine Flow Rate: 2.0 mL/min Flow Rate: 1.5 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 32.0 min Run Time: 32.0 min k'1 = 15.64 k'1 = 3.78 α = 1.33 α = 1.66 reference 55 reference 55

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 61 REGIS Miscellaneous Pharmaceuticals McN 5652 Bupivacaine

McN 5652 SCH3 Bupivacaine 2% IPA/hex w. 0.2% 80:20:0.1 hexane/IPA/TEA diethylamine 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 7-8 min 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 O k'1 = 0.85 k'1 = 1.89 N α = 1.36 α = 1.25 N reference 32 reference 18 N H

Tolperisone p-Chloro-Warfarin Tolperisone p-Chloro-Warfarin 99:1:0.1 hexane/IPA/TEA 85:15:0.1 MeOH/H2O/HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 18 min O Run Time = 12 min OO 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 N Whelk-O 1 CH3 k' = 4.81 k' = 1.64 1 CH3 1 α = 1.10 H3C α = 1.93 OH O reference 18 reference 18

-chloro-warfarin Cl 164 Cyclandelate Indapamide Cyclandelate Iindapamide (mixture of isomers) OH k'1 = 2.46 Cl α O hexane O = 1.68 O 1 ml/min; 254 nm 1:1 hexane/IPA S Run Time = 35 min 1 ml/min; 220 nm NH2 4.6 mm x 25 cm O Run Time = 14 min Whelk-O 1 4.6 mm x 25 cm H reference 18 Whelk-O 1 N O reference 18 N CH3

Column:(S,S)-Whelk-O 1 Column = (R,R)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (60/40) Mobile Phase = (95/5) Ethanol/Hexane + 0.1% Hexane/IPA Triethylamine Flow Rate = 1.0 mL/min Flow Rate: 1.0 mL/min Detection = UV 254 nm Detection: UV 280 nm Run Time = 25.0 min Run Time: 17.0 min k'1 = 3.45 k'1 = 3.78 α = 2.04 α = 1.14 reference 53 reference 56

62 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS Nicardipine Isradipine (reversed phase)

Nicardipine Isradipine (reversed phase) H 73:27:0.1 hexane/IPA/HOAc 63/37 MeOH/H2O H3C N CH3 1 ml/min; 254 nm H 1 ml/min; 254 nm Run Time = 30 min Run Time = 35 min H C N CH 4.6 mm x 25 cm 3 3 4.6 mm x 25 cm O OCH3 Whelk-O 1 Whelk-O 1 O OCH3 k'1 = 6.06 N k'1 = 11.21 O O α α = 1.52 H3C O O = 1.12 N reference 18 reference 18 O

nicardipine NO2 N k' 606

Isradipine (normal phase) SC 41930

Isradipine (normal phase) N SC 41930 98:2:0.5 hexane/IPA/TEA 80:20:0.5 hexane/IPA/HOAc O 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 52 min N Run Time = 6 min 4.6 mm x 25 cm 4.6 mm x 25 cm OO O O Whelk-O 1 Whelk-O 1 H3C k'1 = 9.71 H3C k'1 = 1.05 α O O α = 1.10 = 1.12 OO O reference 18 reference 7 CH3 HO H H3CCHN 3 SC 41930 O H k'1 = 1.05

Hanessian’s Lignan Tropicamide Hanessian's lignan Tropicamide methanol H Column: (R,R)-Whelk-O 1 1 ml/min; 254 nm O 10/100 (FEC) Run Time = 8 min O 25 cm x 4.6 mm 4.6 mm x 25 cm O Mobile Phase: (75/25) Whelk-O 1 Hexane/Ethanol H O k'1 = 0.94 Flow Rate: 1.5 mL/min α = 1.69 Detection: UV 254 nm reference 7 Run Time = 13.9 min H3CO OCH3 k'1 = 4.52 α OCH = 1.49 3 reference 46

U-100057 U-94863 U-100057 U-94863 65:35 hexane/IPA 70:30:0.5 hexane/ Cl NCl 90 ml/min to 34 min, OH IPA/HOAC then 120 ml/min 12 ml/min; 254 nm Run Time = 50 min 2.1 cm x 25 cm O 5.1 cm x 25 cm Whelk-O 1 Whelk-O 1 OO Run Time = 12 min Cl Sample Load = 1.9 g Sample Load = 40 mg reference 37 reference 37

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 63 REGIS Miscellaneous Pharmaceuticals Troglitazone U-94863 Troglitazone U-94863 Column = (S,S)-Whelk-O 1 40:60:0.5 hexane/IPA/HOAc 10/100 (FEC) 1 ml/min; 254 nm Cl NCl 25 cm x 4.6 mm run time = 15 min Mobile Phase = (90/10) 4.6 mm x 25 cm Hexane/IPA Whelk-O 1 O + 0.1% Acetic Acid k'1 = 2.26 Flow Rate = 2.0 mL/min α = 1.95 Cl Detection = UV 220 nm reference 37 k'1 = 13.05 α = 1.22 reference 46

Temazepam Proglumide Column: (S,S)-ULMO Proglumide 25 cm x 4.6 mm 75:25:0.1 hexane/IPA/HOAc Mobile Phase: (97/3) 1 ml/min; 254 nm HO O Hexane/IPA + run time = 10 min 0.1% Acetic acid 4.6 mm x 25 cm Flow Rate: 1.5 mL/min Whelk-O 1 O Detection: UV 254 nm k' = 1.54 1 N Run Time: 31.0 min α = 1.49 N k'1 = 12.05 reference 18 α = 1.34 H O reference 46

30% IPA/hexane O 30% IPA/hexane O 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 1.61 k'1 = 1.66 α = 1.48 N α = 1.69 N reference 44 reference 44

N CH3 N CH3 H H

30% IPA/hexane O 30% IPA/hexane 1 ml/min; 254 nm 1 ml/min; 254 nm O 4.6 mm x 25 cm Whelk-O 1 4.6 mm x 25 cm Whelk-O 1 k'1 = 1.29 k'1 = 2.56 α = 1.83 N α = 1.25 reference 44 reference 44 N N N CH3 H O2N H

64 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS

30% IPA/hexane 30% IPA/hexane O 1 ml/min; 254 nm O 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 N k'1 = 1.38 N k'1 = 1.34 α = 1.44 α = 1.60 reference 44 reference 44 Cl N N CH3 Cl H H

30% IPA/hexane O 30% IPA/hexane O 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 N Whelk-O 1 N k'1 = 1.29 k'1 = 1.37 α = 1.83 α = 1.90 reference 44 reference 44 N N H H

F Cl

30% IPA/hexane O 30% IPA/hexane O 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 N Whelk-O 1 N k'1 = 1.18 k'1 = 1.34 α = 1.72 α = 1.78 reference 44 reference 44 Cl N Cl N H H

F Cl

70:30:05 hexane/ 70:30:05 hexane/ O 2-propanol/diethyl amine O 2-propanol/diethyl amine 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 N N k'1 = 2.36 k'1 = 1.70 α = 1.33 α = 1.55 reference 44 reference 44 N N N N CH3 H H F

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 65 REGIS Miscellaneous Pharmaceuticals

70:30:05 hexane/ O 70:30:05 hexane/ O 2-propanol/diethyl amine 2-propanol/diethyl amine 1 ml/min; 254 nm 1 ml/min; 254 nm 4.6 mm x 25 cm 4.6 mm x 25 cm N Whelk-O 1 N Whelk-O 1 k'1 = 1.90 k'1 = 1.73 α = 1.45 α = 1.59 N reference 44 N N reference 44 N H H

Cl

40% IPA/hexane 10% IPA/hexane 1 ml/min 1 ml/min 4.6 mm x 25 cm H3CO 4.6 mm x 25 cm O OO (S,S) Whelk-O 1 (S,S) Whelk-O 1 OH α = 1.34 α = 1.29 Rs = 2.10 OCH Rs = 2.10 N 3 H reference 45 N reference 45 H N N O N

H 10% IPA/hexane 50% IPA/hexane 1 ml/min 1 ml/min N 4.6 mm x 25 cm OO 4.6 mm x 25 cm (S,S) Whelk-O 1 O (S,S) Whelk-O 1 O OCH3 α = 1.10 α = 1.32 N Rs = 0.95 H Rs = 2.10 N reference 45 reference 45 H N H N O H

45% IPA/hexane O 45% IPA/hexane 1 ml/min 1 ml/min O 4.6 mm x 25 cm N H 4.6 mm x 25 cm (S,S) Whelk-O 1 (S,S) Whelk-O 1 H α = 2.17 N H α = 1.57 N Rs = 2.20 N Rs = 2.20 reference 45 reference 45 N O H

Br

66 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS

10% IPA/hexane 10% IPA/hexane Br 1 ml/min Cl 1 ml/min H3C 4.6 mm x 25 cm 4.6 mm x 25 cm (S,S) Whelk-O 1 H (S,S) Whelk-O 1 α = 1.04 α = 1.04 Rs = 0.60 Rs = 0.60 reference 45 reference 45 O N O N H H CH CH3 3

15% IPA/hexane 40% IPA/hexane CH3 1 ml/min 1 ml/min O O 4.6 mm x 25 cm 4.6 mm x 25 cm N (S,S) Whelk-O 1 F (S,S) Whelk-O 1 α = 1.13 α = 1.22 O N N CH3 Rs = 1.50 Rs = 1.50 H reference 45 reference 45 O

OCH3 H2N

Bendroflumethiazide 10% IPA/hexane Bendroflumethiazide 1 ml/min OCH3 Column = (R,R)-ULMO 4.6 mm x 25 cm 25 cm x 4.6 mm O O O O (S,S) Whelk-O 1 O Mobile Phase = (75/25) α Cl S S H = 1.11 O Hexane/IPA H2N N Rs = 1.50 Flow Rate = 1.0 mL/min reference 45 Detection = UV 254 nm F3C N F3CN Run Time = 18 min H k'1 = 2.99 HO α = 1.84 reference 46

Indapamide Thalidomide Indapamide Thalidomide Column = (R,R)-ULMO Column = (R,R)-ULMO Cl 25 cm x 4.6 mm H 25 cm x 4.6 mm Mobile Phase = (75/25) Mobile Phase: (90/10) N Hexane/IPA N NH2 Hexane/IPA + 0.1% Flow Rate = 1.0 mL/min S Acetic acid O OO

Detection = UV 254 nm CH3 Flow Rate = 1.0 mL/min Run Time = 16 min Detection = UV 220 nm k'1 = 3.09 Run Time = 28.0 min α = 1.58 k'1 = 7.71 reference 46 α = 1.22 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 67 REGIS Miscellaneous Pharmaceuticals Warfarin Chlorthalidone Warfarin Chlorthalidone Column: (S,S)-ULMO Column = (S,S)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (70/30) Mobile Phase = (99/1)

Heptane/IPA + 0.1% TFA CH2Cl2/CH3OH + Flow Rate: 1.0 mL/min 0.01 M Ammonium Acetate Detection: UV 230 nm Flow Rate = 1.5 mL/min Run Time: 6.5 min Detection = UV 254 nm k'1 = 0.89 Run Time = 20.0 min α = 1.36 k'1 = 9.38 reference 48 α = 1.18 reference 46

Flobufen Metabolites Flobufen and Flobufen Metabolites Flobufen Metabolites Flobufen and Flobufen Column = (S,S)-ULMO Metabolites 25 cm x 4.6 mm Column = (S,S)-ULMO Mobile Phase = (97/3) 25 cm x 4.6 mm Heptane/Glyme + Mobile Phase = (90/10) 0.1% TFA Heptane/IPA + 0.1% TFA Flow Rate = 1.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 215 nm α = 1.08 Detection = UV 230 nm α = 1.20 α = 1.14 Run Time = 21.0 min α Run Time = 24.0 min α = 1.14 reference 47 = 1.14 reference 47

Dexmedetomidine (Enriched) 4(3H)-Quinazolone Derivatives Dexmedetomidine (Enriched) 4(3H)-Quinazolone Derivatives Column = (S,S)-Whelk-O 2 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (90/10) Mobile Phase = (80/20) Hexane/Ethanol Hexane/Ethanol + 10 mM Ammonium Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 225 nm Detection = UV 220 nm Run Time = 16.0 min k'1 = 3.41 k'1 = 2.88 α = 1.39 α = 1.56 reference 46 reference 58

4(3H)-Quinazolone Derivatives 4(3H)-Quinazolone Derivatives 4(3H)-quinazolone 4(3H)-quinazolone derivatives derivatives Column = (S,S)- Column = (S,S)- Whelk-O 1 Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (90/10) Mobile Phase = (80/20) Hexane/IPA Hexane/Ethanol Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 225 nm Detection = UV 225 nm Run Time = 15.0 min Run Time = 17.0 min k'1 = 3.54 k'1 = 2.95 α = 1.19 α = 1.62 reference 58 reference 58

68 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS 4(3H)-Quinazolone Derivatives 4(3H)-Quinazolone Derivatives 4(3H)-Quinazolone Derivatives 4(3H)-Quinazolone Derivatives Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (80/20) Mobile Phase = (80/20) Hexane/Ethanol Hexane/Ethanol Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 225 nm Detection = UV 225 nm Run Time = 21.0 min Run Time = 15.0 min k'1 = 3.75 k'1 = 3.19 α = 1.57 α = 1.37 reference 58 reference 58

Ifenprodil Ketamine Ifenprodil Ketamine Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (85/15) Mobile Phase = (99/1) Hexane/IPA + Hexane/IPA + 0.1% TEA 0.01 M Ammonium Acetate Flow Rate = 1.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 220 nm Run Time = 22.0 min Run Time = 16.5 min k'1 = 6.37 k'1 = 6.16 α = 1.14 α = 1.32 reference 46 reference 46 Tofisopam and it’s Conformers Ketoconazole Tofisopam and it’s Conformers Ketoconazole Column = (R,R)-β-Gem 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) Mobile Phase = (70/30) 25 cm x 4.6 mm Hexane/Ethanol + 0.1% TEA Mobile Phase = (46/46/8) Flow Rate = 1.0 mL/min CH2Cl2/Hexane/IPA + Detection = UV 254 nm 0.01 M Ammonium Acetate Run Time = 25.0 min Flow Rate = 1.5 mL/min Detection = UV 254 nm k'1 = 2.66 α = 3.13 Run Time = 16.0 min reference 46 k'1 = 6.60 α = 1.19 reference 46 Coumachlor Sulpiride Coumachlor Sulpiride Column = (R,R)-Whelk-O 1 Column = (R,R)-DACH-DNB 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (65/35) Mobile Phase = (95/5)

Hexane/Ethanol + CH2Cl2/Ethanol + 0.1% Acetic Acid 0.01 M Ammonium Acetate Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 10.0 min Run Time = 14.0 min k'1 = 1.48 α k'1 = 5.92 = 2.90 α = 1.24 reference 46 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 69 REGIS Miscellaneous Pharmaceuticals Ofloxacin Isoxsuprine Ofloxacin Isoxsuprine Column = (S,S)-Whelk-O 1 Column = (R,R)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (43/43/14) Mobile Phase = (95/5)

CH2Cl2/Hexane/Ethanol + Hexane/Ethanol + 0.01 M Ammonium Acetate 0.01 M Flow Rate = 1.5 mL/min Ammonium Acetate Detection = UV 254 nm Flow Rate = 2.0 mL/min Run Time = 10.0 min Detection = UV 220 nm k'1 = 2.96 Run Time = 28.0 min α = 1.24 k'1 = 17.91 reference 46 α = 1.08 reference 46 Warfarin (Normal Phase) Warfarin (Reversed Phase) Warfarin (normal phase) Warfarin (reversed phase) Column = (R,R)- Column = (R,R)- Whelk-O 1 Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase =

(65/35) Hexane/IPA (70/30) CH3OH/H2O + 0.1% Acetic Acid + 0.1% Acetic Acid Flow Rate = 1.0 mL/min Flow Rate = 1.0 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 11.5 min Run Time = 15.0 min k'1 = 1.54 k'1 = 3.54 α = 2.07 α = 1.55 reference 46 reference 46 Cromakalim Trichlormethiazide Cromakalim Trichlormethiazide Column = (R,R)-Whelk-O 1 Column = (R,R)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (92/8) Mobile Phase = Hexane/Ethanol (75/25) Flow Rate = 1.5 mL/min Hexane/IPA + Detection = UV 254 nm 0.1% Acetic Acid Run Time = 21.0 min Flow Rate = 1.5 mL/min k'1 = 9.18 Detection = UV 254 nm α = 1.14 Run Time = 15.0 min reference 46 k'1 = 5.16 α = 1.43 reference 46 Temazepam Prilocaine Temazepam Prilocaine Column = (S,S)-Whelk-O 1 Column = (S,S)-ULMO 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase = (99/1) Hexane/ (80/20) Hexane/IPA Ethanol + 0.01 + 0.1% Acetic Acid M Ammonium Acetate Flow Rate = 2.0 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 13.0 min Run Time = 15.0 min k'1 = 6.86 k'1 = 5.70 α = 1.34 α = 1.28 reference 46 reference 46

70 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS Lorazepam Althiazide Lorazepam Althiazide Column = (R,R)-Whelk-O 1 Column = (S,S)-ULMO 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (70/30) Mobile Phase = (75/25) Hexane/IPA + Hexane/IPA + 0.1% Acetic Acid 0.1% Acetic Acid Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Dtection - UV 254 nm Detection = UV 254 nm Run Time = 9.0 min Run Time = 13.0 min k'1 = 2.08 k'1 = 3.94 α = 2.02 α = 1.53 reference 46 reference 46

Clenbuterol Metolazone Clenbuterol Metolazone Column = (R)-α-Burke 2 Column = (R,R)- 25 cm x 4.6 mm Whelk-O 1 Mobile Phase = (90/10) 25 cm x 4.6 mm

CH2Cl2/Ethanol + Mobile Phase = 0.01 M Ammonium (55/45) Acetate Hexane/Ethanol Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 12.0 min Run Time = 10.0 min k'1 = 4.99 k'1 = 1.93 α = 1.09 α = 2.43 reference 46 reference 46 Methadone Hydrochloride Ethotoin Methadone Hydrochloride Ethotoin Column = (S)-α-Burke 2 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase = (88/12) (75/25) Hexane/Ethanol Hexane/Ethanol + 0.1% TEA Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Dtection - UV 254 nm Detection = UV 254 nm Run Time = 11.0 min Run Time = 10.0 min k'1 = 1.65 k'1 = 3.50 α = 3.03 α = 1.34 reference 46 reference 46 Zopiclone Lansoprazole Zopiclone Lansoprazole Column = (R,R)-Whelk-O 1 Column = (S)-α-Burke 2 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (95/5) Mobile Phase =

CH2Cl2/Ethanol (94/3/3)

+ 0.01 M CH2Cl2/Ethanol/Methanol Ammonium Acetate + 0.2% Acetic Acid Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 8.5 min Run Time = 6.0 min k'1 = 1.94 k'1 = 0.88 α = 2.01 α = 2.43 reference 46 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 71 REGIS Miscellaneous Pharmaceuticals Chlormezanone Tetrabenazine Chlormezanone Tetrabenazine Column = (R,R)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) Mobile Phase = (60/40) 25 cm x 4.6 mm Hexane/IPA Mobile Phase = Flow Rate = 1.5 mL/min (55/45) Hexane/IPA Detection = UV 254 nm + 0.1% TFA Run Time = 13.0 min Flow Rate = 1.5 mL/min k'1 = 4.48 Detection = UV 280 nm α = 1.36 Run Time = 13.4 min reference 46 k'1 = 3.35 α = 1.93 reference 46 Dihydrotetrabenazine trans-U-50488H Dihydrotetrabenazine trans-U-50488H Column = (S,S)-Whelk-O 1 Column = (3R,4S)-Pirkle I-J 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (92/8) Mobile Phase = Hexane/Ethanol + (60/40) Hexane/IPA 0.01 M Ammonium + 0.1% TFA Acetate Flow Rate = 1.5 mL/min Flow Rate = 2.0 mL/min Detection = UV 280 nm Detection = UV 220 nm Run Time = 9.3 min Run Time = 12.0 min k'1 = 2.50 k'1 = 6.71 α = 1.65 α = 1.27 reference 46 reference 46 Fluridil Alfuzosin Fluridil Alfuzosin Column = (S,S)-Whelk-O 2 Column = (R,R)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) Mobile Phase = 25 cm x 4.6 mm (57/43) Mobile Phase = (68/28/4)

H2O/CH3OH Hexane/CH2Cl2/ Flow Rate = 1.5 mL/min Ethanol + 4 mM Detection = UV 254 nm Ammonium Acetate k'1 = 12.9 Flow Rate = 2.0 mL/min α = 1.18 Detection = UV 254 nm reference 46 k'1 = 7.37 α = 1.15 reference 46 Doxazosin Pazufloxacin Doxazosin Pazufloxacin Column = (S,S)-Whelk-O 1 Column = (S,S)-Whelk-O 1 10/100 (FEC) 25 cm x 4.6 mm 10/100 (FEC) 25 cm x 4.6 mm Mobile Phase = (66/29/5) Mobile Phase = (40/40/20) Hexane/CH2Cl2/ CH2Cl2/Hexane/IPA Ethanol + 5 mM + 0.15% TFA Ammonium Acetate Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 6.7 min k'1 = 14.2 k'1 = 1.71 α = 1.13 α = 1.58 reference 46 reference 46

72 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Miscellaneous Pharmaceuticals REGIS Mosapride Modafinil Mosapride Modafinil Column = (R,R)- Column = (S,S)-Whelk-O 1 Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (65/35) Mobile Phase = (66/28/6) Hexane/IPA

Hexane/CH2Cl2/Ethanol Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm k'1 = 3.57 k'1 = 7.37 α = 1.75 α = 1.19 reference 46 reference 46

Sulindac Nadifloxacin Sulindac Nadifloxacin Column = (R,R)-Whelk-O 1 Column = (S,S)-Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (48/48/4) Mobile Phase = (45/45/10)

Hexane/CH2Cl2/IPA CH2Cl2/Hexane/IPA + 0.1% Acetic acid + 10 mM Ammonium Flow Rate = 1.5 mL/min Acetate Detection = UV 254 nm Flow Rate = 1.5 mL/min k'1 = 4.32 Detection = UV 254 nm α = 1.45 k'1 = 2.95 reference 46 α = 1.58 reference 46 Lorglumide Idazoxan Lorglumide Idazoxan Column = (R,R)-Whelk-O 1 Column = (S,S)-Whelk-O 1 10/100 (FEC) 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (70/29/1) Mobile Phase = (95/5) Hexane/Methylene Hexane/IPA Chloride/IPA + 0.1% Acetic Acid + 0.1% TEA Flow Rate = 2.0 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Dtection - UV 254 nm k'1 = 5.22 k'1 = 5.86 α = 1.25 α = 1.23 reference 46 reference 46

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 73 REGIS Barbiturates Hexobarbital Hexobarbital 5% EtOH/Hexane CH3 0.7 ml/min; 254nm run time = 16 min N ONa 4.6 mm x 25 cm L-Leucine H3C k'1 = 2.89 N α = 1.10

O

Diol Epoxides REGIS Ureas REGIS r-7,t-8-Dihydroxy-t-9, 10-epoxy-7,8,9, 1-Naphthylureaphenethylamine 10-tetrahydrobenzo[a]pyrene 1-Naphthylureaphenethylamine 30% EtOH/Hexane r-7,t-8-Dihydroxy-t-9, 10-epoxy-7,8,9, 4.6 mm x 25 cm 10-tetrahydrobenzo[a]pyrene D-Phenyglycine 40% EtOH/Hexane 1 ml/min; 254 nm 4.6 mm x 25 cm (R,R) β-Gem 1 Run Time = 10 min 1 ml/min; 254 nm k'1 = 2.37 O H CH3 Run Time = 14 min α = 1.22 k'1 = 3.18 α = 1.25 HN C N CH O

HO OH

74 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Natural Products REGIS Flavanone 2-cis-4-trans-Abscisic Acid (ABA) Flavanone O 2-cis-4-trans-Abscisic Acid (ABA) 1% IPA/hexane 80:20:0.5 hexane/IPA/HOAc 1 ml/min; 254 nm 1 ml/min; 254 nm Run Time = 25 min Run Time = 5 min H3C CH3 CH3 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 O Whelk-O 1 k'1 = 7.08 k'1 = 1.58 OH α = 1.04 flavanone α = 1.39 reference 26 reference 9 O HO O k'1 =708

2-trans-4-trans-Abscisic Acid ABA Methyl Ester 2-trans-4-trans-Abscisic ABA Methyl Ester Acid (ABA) 80:20:0.5 80:20:0.5 Hexane/IPA/HOAc CH OH Hexane/IPA/HOAc H3C CH3 3 1 ml/min; 254 nm H C CH CH3 OH 1 ml/min; 254 nm Run Time = 5 min 3 3 Run Time = 5 min O 4.6 mm x 25 cm O 4.6 mm x 25 cm OH Whelk-O 1 OH Whelk-O 1 k' = 2.41 O 1 k'1 = 2.08 α = 1.31 O OO α = 1.21 reference 9 CH reference 9 3

Combretastatin D-1 Combretastatin D-1 Combretastatin D-1 Combretastatin D-1 20% IPA/Hexane OH semi-prep separation OH 2 ml/min; 254 nm 20% IPA/hexane O run time = 13 min O 2 ml/min; 300 nm 4.6 mm x 25 cm 200 µl of 12.7 mg/ml soln Whelk-O 1 load = 2.5 mg k'1 = 4.54 O run time = 10 min O α = 1.45 4.6 mm x 25 cm reference 17 Whelk-O 1 O reference 17 O O O

Calanolide A Calanolide A (semi prep) Calanolide A Calanolide A (semi prep) 10% IPA/hexane 10% IPA/hexane 1.25 ml/min; 270 nm 1.25 ml/min; 270 nm run time = 18 min O run time = 18 min O 4.6 mm x 25 cm 4.6 mm x 25 cm Whelk-O 1 Whelk-O 1 k'1 = 3.2 5 mg sample α = 1.4 k' = 3.2 1 OOO reference 16 OOO α = 1.4 reference 16 OH OH

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 75 REGIS Natural Products Abscisic Acid Tetrahydropalmatine Abscisic Acid Tetrahydropalmatine Column = (R,R)-Whelk-O 1 Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) Mobile Phase = (85/15) 25 cm x 4.6 mm Hexane/IPA + Mobile Phase = (50/50) 0.1% Acetic Acid Hexane/IPA Flow Rate = 1.5 mL/min Flow Rate = 1.5 mL/min Detection = UV 254 nm Detection = UV 254 nm Run Time = 11.0 min k'1 = 6.66 k'1 = 3.52 α = 1.46 α = 1.38 reference 46 reference 46

Taxifolin Luciferin Taxifolin Luciferin Column = (S,S)-Whelk-O 2 Column = L-Leucine 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (60/40) Mobile Phase = (85/15) Hexane/Ethanol + 0.04 mM Hexane/Ethanol Ammonium Acetate + 0.1% TFA Flow Rate = 1.5 mL/min Flow Rate = 2.0 mL/min Detection = UV 254 nm Detection = UV 220 nm Run Time = 15.5 min k'1 = 11.87 k'1 = 6.09 α = 1.20 α = 1.25 reference 46 reference 46

REGIS β−Blockers β-Blocker Bambuterol β-blocker Bambuterol Column: (S,S)-DACH-DNB Column = (R,R)-alpha-Burke 2 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase: (92/8) Mobile Phase = (40/40/20) CH2Cl2/IPA Hexane/Methylene Flow Rate: 1.0 mL/min Chloride/Ethanol + 20 mM Detection: UV 254 nm Ammonium Acetate Run Time: 11.0 min Flow Rate = 1.5 mL/min k’1: 2.27 Detection = UV 254 nm α : 1.42 k'1 = 3.74 reference 59 α = 1.35 reference 46

76 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ β−Blockers REGIS Alprenolol Betaxolol Alprenolol Betaxolol 90:5:5 CH2C12/EtOH/MeOH 85:10:5 CH2C12/EtOH/MeOH 10 mM NH4OAc 10 mM NH4OAc O 1 ml/min; 254 nm 1 ml/min; 254 nm run time = 10 min run time = 11 min 4.6 mm x 25 cm 4.6 mm x 25 cm α-Burke 2 O N α-Burke 2 k' = 1.44 k' = 2.36 1 1 O N α = 1.44 OH H α = 1.25 reference 33 reference 33 OH H

Atenolol Bupranolol

Atenolol H2N Bupranolol 85:10:5 Column: (3R,4S)-Pirkle 1-J

CH2C12/EtOH/MeOH O 25 cm x 4.6 mm 15 mM NH4OAc O N Mobile Phase: (85/15) 1 ml/min; 254 nm CH2Cl2/Ethanol run time = 16 min OH H + 0.015M 4.6 mm x 25 cm Ammonium Acetate α-Burke 2 Flow Rate: 1.0 mL/min k'1 = 4.41 Detection: UV 254 nm α = 1.13 Run Time: 8.5 min reference 33 k’1: 1.44 α: 1.47 reference 46 Bufuralol Metoprolol Bufuralol metoprolol Column: (3R,4S)-Pirkle 1-J 85:10:5 CH2C12/EtOH/MeOH 25 cm x 4.6 mm 10 mM NH4OAc Mobile Phase: (90/10) O 1 ml/min; 254 nm CH3 CH2Cl2/Ethanol run time = 13 min + 0.02 M Ammonium 4.6 mm x 25 cm Acetate α-Burke 2 Flow Rate: 1.0 mL/min k'1 = 2.66 Detection: UV 254 nm α = 1.28 O N Run Time: 7.0 min reference 33 OH H k’1: 0.91 α: 2.01 reference 46 Tulobuterol HCI β-Blocker Tulobuterol HCI β-Blocker Column: (S)-α-Burke 2 Column: (S,S)- 25 cm x 4.6 mm DACH-DNB Mobile Phase: (91/9) 25 cm x 4.6 mm CH2Cl2/Ethanol Mobile Phase: + 0.01 M (90/10) Ammonium Acetate CH2Cl2/IPA Flow Rate: 1.5 mL/min Flow Rate: 1.0 mL/min Detection: UV 254 nm Detection: UV 254 nm Run Time: 15.0 min Run Time: 18.0 min k’1: 6.38 k'1: 4.52 α: 1.13 α: 1.29 reference 46 reference 59

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 77 REGIS β−Blockers Nadolol Timolol Maleate Nadolol Timolol Maleate Column = (S,S)-Whelk-O 1 Column = (3R,4S)-Pirkle 1-J 10/100 (FEC) 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = (78/22) Mobile Phase =

Hexane/Ethanol + (94/3/3) CH2Cl2/ 0.01 M Ammonium Ethanol/IPA Acetate + 0.01M Ammonium Acetate Flow Rate = 1.5 mL/min Flow Rate = 1.0 mL/min Detection = UV 270 nm Detection = UV 294 nm Run Time = 9.5 min Run Time = 16.0 min k'1 = 3.05 k'1 = 3.72 α = 1.43 α = 1.33 reference 46 reference 46 Carazolol Pindolol Carazolol Pindolol Column = (R)-α-Burke 2 Column: (3R,4S)-Pirkle 1-J 25 cm x 4.6 mm 25 cm x 4.6 mm Mobile Phase = Mobile Phase: (80/20) (46/46/8) CH Cl / 2 2 CH2Cl2/Ethanol + 0.04M Methanol/Ethanol + 0.01 M Ammonium Acetate Ammonium Acetate Flow Rate: 1.0 mL/min Flow Rate = 1.5 mL/min Detection: UV 254 nm Detection = UV 254 nm Run Time: 11.0 min Run Time = 15.0 min k’1: 1.56 k'1 = 6.73 α: 2.06 α = 1.10 reference 46 reference 46 Practolol Oxprenolol Practolol Oxprenolol 85:10:5 CH2C12/ Column: (3R,4S)-Pirkle 1-J EtOH/MeOH H3C O 25 cm x 4.6 mm 15 mM NH4OAc Mobile Phase: (90/10) N 1 ml/min; 254 nm H CH2Cl2/Ethanol + 0.015M run time = 19 min Ammonium Acetate 4.6 mm x 25 cm O N Flow Rate: 1.0 mL/min α-Burke 2 practolol OH H Detection: UV 254 nm k'1 = 4.78 Run Time: 13.5 min α = 1.14 k’1: 3.55 reference 33 α: 1.15 reference 46

Pronethalol Propranolol Pronethalol Propranolol 90:10 CH2C12/EtOH Column: (3R,4S)-Pirkle 1-J 15 mM NH4OAc 25 cm x 4.6 mm 1 ml/min; 254 nm Mobile Phase: (80/20)

run time = 15 min CH2Cl2/Ethanol + 0.04M 4.6 mm x 25 cm Ammonium Acetate α -Burke 2 N Flow Rate: 1.0 mL/min k'1 = 3.26 Detection: UV 254 nm α = 1.31 OH H Run Time: 6.5 min

reference 33 k’1: 0.80 α: 1.80 reference 46

78 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Amino Acids REGIS Norleucine 4-Fluorophenyalanine Norleucine 4-Fluorophenyalanine Column: ChiroSil® RCA(+) Column: ChiroSil® RCA(+) or or SCA(-) SCA(-) 15 cm x 4.6 mm 15 cm x 4.6 mm Mobile Phase: (70/30)

Mobile Phase: CH3OH/H2O+10 (45/55) CH3OH/H2O mM Acetic acid +10 mM Acetic acid Flow Rate: 1.5 mL/min Flow Rate: 1.0 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 9.6 min Run Time: 5.6 min k'1: 2.92 k'1: 1.28 α: 2.56 α: 1.75

1,2,3,4-Tetrahydro-1-naphthylamine Arginine 1,2,3,4-Tetrahydro-1-naphthylamine Arginine Column: ChiroSil® RCA(+) Column: ChiroSil® or SCA(-) 15 cm x 4.6 mm RCA(+) or SCA(-) Mobile Phase: (84/16) 15 cm x 4.6 mm

CH3OH/H2O Mobile Phase: +10 mM H2SO4 and (84/16) CH3OH/H2O 0.1% TEA +10 mM H2SO4 Flow Rate: 1.0 mL/min Flow Rate: 0.8 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 3.5 min Run Time: 4.9 min k'1: 0.82 k'1: 1.21 α: 1.76 α: 1.64

1-Aminoindan Tyrosine 1-Aminoindan Tyrosine Column: ChiroSil® Column: ChiroSil® RCA(+) or SCA(-) RCA(+) or SCA(-) 15 cm x 4.6 mm 15 cm x 4.6 mm Mobile Phase: (84/16) Mobile Phase:

CH3OH/H2O (70/30) CH3OH/H2O +5 mM HClO4 +10 mM Acetic acid Flow Rate: 1.0 mL/min Flow Rate: 1.5 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 4.8 min Run Time: 9.1 min k'1: 1.44 k'1: 2.95 α: 1.91 α: 2.38

Methionine Leucine Methionine Leucine Column: ChiroSil® RCA(+) Column: ChiroSil® or SCA(-) 15 cm x RCA(+) or SCA(-) 4.6 mm 15 cm x 4.6 mm Mobile Phase: Mobile Phase:

(45/55) CH3OH/H2O (45/55) CH3OH/H2O +10 mM Acetic acid +10 mM Acetic acid Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 7.5 min Run Time: 5.5 min k'1: 1.64 k'1: 1.03 α: 2.04 α: 2.14

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 79 REGIS Amino Acids Glutamine Kynurenine Glutamine Kynurenine Column: ChiroSil® SCA(-) Column = (S,S)-Whelk-O 1 25 cm x 4.6 mm 10/100 (FEC) 25 cm x 4.6 mm Mobile Phase: Mobile Phase =

(65/35) CH3CN/H2O (65/35) +0.01% Acetic acid H2O/CH3OH + Flow Rate: 1.5 mL/min 0.1% Acetic Acid Detection: UV 210 nm Flow Rate = 1.0 mL/min Run Time: 6.5 min Detection = UV 254 nm k'1: 1.51 Run Time = 9.0 min α: 1.61 k'1 = 1.17 reference 46 α = 1.99 reference 46 D,L-p-Hydroxy-Phenylglycine Tryptophan D,L-p-Hydroxy-Phenylglycine Tryptophan Column: ChiroSil®-SCA(+) Column: ChiroSil® 15 cm x 4.6 mm RCA(+) or SCA(-) Mobile Phase: 15 cm x 4.6 mm (50/50) CH3ON/H2O Mobile Phase: (70/30) +0.02% Acetic acid CH3OH/H2O Flow Rate: 1.0 mL/min +10 mM Acetic acid Detection: UV 210 nm Flow Rate: 1.5 mL/min Run Time: 11.0 min Detection: UV 210 nm k'1: 2.11 Run Time: 11.0 min α : 2.29 k'1: 4.06 reference 46 α: 2.15

Serine Phenylalanine Serine Phenylalanine Column: ChiroSil® RCA(+) Column: ChiroSil® RCA(+) or or SCA(-) SCA(-) 15 cm x 4.6 mm 15 cm x 4.6 mm Mobile Phase: (70/30)

Mobile Phase: CH3OH/H2O (84/16) CH3OH/H2O +10 mM Acetic acid +5 mM HClO4 Flow Rate: 1.5 mL/min Flow Rate: 0.8 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 8.9 min Run Time: 6.0 min k'1: 2.66 k'1: 1.37 α: 2.57 α: 1.99

Phenylglycine Norvaline Phenylglycine Norvaline Column: ChiroSil® RCA(+) Column: ChiroSil® RCA(+) or or SCA(-)15 cm x 4.6 mm SCA(-)15 cm x 4.6 mm Mobile Phase: (70/30) Mobile Phase:

CH3OH/H2O (45/55) CH3OH/H2O +10 mM H2SO4 and +10 mM Acetic acid 0.1% TEA Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 5.3 min Run Time: 13.1 min k'1: 1.15 k'1: 3.14 α: 1.79 α: 2.60

80 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Amino Acids REGIS Histidine Glutamic Acid Histidine Glutamic Acid Column: ChiroSil® Column: ChiroSil® RCA(+) or SCA(-) RCA(+) or SCA(-) 15 cm x 4.6 mm 15 cm x 4.6 mm Mobile Phase: Mobile Phase:

(45/55) CH3OH/H2O (65/35) CH3OH/H2O +10 mM Acetic acid +0.05% Phosphoric acid Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 26.0 min Run Time: 4.5 min k'1: 10.96 k'1: 0.71 α: 1.27 α: 2.27

DOPA Ethionine DOPA Ethionine Column: ChiroSil® Column: ChiroSil® RCA(+) or SCA(-) RCA(+) or SCA(-) 15 cm x 4.6 mm 15 cm x 4.6 mm Mobile Phase: Mobile Phase:

(70/30) CH3OH/H2O (75/25) CH3OH/H2O +0.01% Phosphoric acid +0.02% Acetic acid Flow Rate: 1.0 mL/min Flow Rate: 1.0 mL/min Detection: UV 210 nm Detection: UV 210 nm Run Time: 5.5 min Run Time: 6.2 min k'1: 0.97 k'1: 1.29 α: 2.30 α: 2.07

Lysine Lysine Column: ChiroSil® RCA(+) or SCA(-) 15 cm x 4.6 mm Mobile Phase:

(70/30) CH3OH/H2O +0.01% Phosphoric acid Flow Rate: 1.0 mL/min Detection: UV 210 nm Run Time: 5.3 min k'1: 1.44 α: 1.48

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 81 Frequently Asked Questions ABOUT PIRKLE-TYPE CHIRAL STATIONARY PHASES AND COLUMNS FROM REGIS hroughout the past 20 years, the Sales and Technical persons at Do you always need a modifier in the mobile phase? TRegis have fielded hundreds of different questions related to our No modifiers are usually needed for initial method development. Chiral Stationary Phases (CSP’s). Listed here you will find some of Modifiers can be used to improve peak shape and resolution when the frequently asked questions. By no means is this a complete list, the samples are extremely basic or acidic in nature. Acetic acid or if you have questions regarding chiral chromatography, please feel ammonium acetate are recommended for acidic compounds, and free to contact Regis directly or pass your question on through one triethylamine, diethylamine or ammonium acetate are of our distributors. recommended for basic compounds. Usually 0.1% of modifier is all that is required. Note: Although TFA may be used as a modifier, What is the pressure rating of your columns? its use should be limited. Acetic acid usually works as well as TFA. All analytical (25cm x 4.6 mm i.d.) and semi-preparative (25cm x 10.0 mm i.d.) columns manufactured by Regis can Can I use your columns for SMB chromatography and SFC? tolerate pressures up to 6000 psi. Larger columns will tolerate Yes, many analytical and preparative chromatographers use 3000 psi. It is very important not to exceed the maximum pressure Pirkle-Type Chiral columns in both SFC and SMB. Special rating for any HPLC column as you may disrupt the integrity of the hardware is necessary for certain column dimensions. silica bed and destroy the column. What is the difference between Whelk-O 1 and Whelk-O 2? Can Regis columns be reversed? Although the Whelk-O 1 and Whelk-O 2 both share the same Yes, all columns packed by Regis are fully reversible. In fact, Regis Chiral selector, they have distinct differences. The Whelk-O 1 is was the first column manufacturer to sell a fully reversible HPLC monofunctionally bonded to silica and the Whelk-O 2 is column. It is recommended to reverse your column frequently. This trifunctionally bonded. The Whelk-O 2 was designed to tolerate helps keep the frit surface from becoming clogged with undissolved strong acidic modifiers such as TFA. The Whelk-O 2 was designed sample or particulates in the mobile phase, thus extending the for preparative use and is not available on 5-micron silica. Due to column life. the fact the Whelk-O 2 is a trifunctional bond, coverage on the silica will be less than with Whelk-O 1. This decrease in the actual number What is the pH range of your columns? of bonded sites will decrease selectivity and not allow for exact All of Regis’ Chiral phases are bonded on silica. The recommended reproducibility of a method developed on a Whelk-O 1 column. pH range is 2.5 to 7.5. Limited usage outside of this pH range can be tolerated, but it has been proven that extended usage outside of Does my compound need an aromatic ring to achieve the range will decrease column life. separation on a Pirkle-Type Chiral column? In most cases (not all), yes. Chiral recognition occurs at binding Can your columns be used in normal and reversed-phase sites. The potential π-π interaction that can occur between the solvents? aromatic rings on the Chiral selector and the aromatic ring on the Yes, all Pirkle-Type Chiral HPLC columns can be used in BOTH sample is a major factor in achieving selectivity. Binding does normal and reversed-phase solvents. Generally, the Pirkle-Type occur at other sites such as acidic sites, basic sites and steric CSP’s will give better separations by using them with normal-phase interaction sites—this is why you do not always need a ring—but solvents. There are numerous examples, however; where by far, the π-π interaction is the major binding site. separations with reversed-phase solvents will outperform those with normal-phase solvents. Can I use the Pirkle-Type Chiral columns in polar organic mode? Yes, even though the success rate is very poor, you can use the Can I use the same column for reversed-phase and normal- columns in polar organic mode. We do not recommend dedicating phase solvent systems while doing method development? a slot in your method development station for a Pirkle-Type Chiral Yes, just make sure you completely flush out the column with a column if you are exclusively running in polar organic mode. Add miscible solvent such as IPA or ethanol. We recommend at least another Pirkle-Type column to your normal-phase system to 20 column volumes. achieve a higher success rate.

How long does it take your columns to equilibrate? What sampling loading can I expect from Pirkle-Type Chiral The column should equilibrate after about 20 column volumes. HPLC columns? When you are switching from normal to reversed-phase solvent The typical loading range – with relative retention’s (alpha) greater systems and vise-versa, flush the column with a miscible solvent for than 1.3—is ~ 4-16 mg of sample per gram of packing. Below are 20 column volumes. It should take another 20 column volumes to typical loadings for some of the different column sizes: Note: equilibrate. The equilibration volumes may vary depending on the Factors, such as solubility, will greatly affect loading capacity. composition of the mobile phase. Analytical column, 25cm x 4.6mm, ~ 3.5 grams of packing, loading is 14-56 mg/ injection. What type of silica do you use? Semi-prep column, 25cm x 10.0mm, ~ 16 grams of packing, Regis exclusively uses Exsil® for our 5-micron material and loading is 64-256 mg/ injection. Kromasil‚ for 10 and 16-micron material. Both brands of silica are Prep column, 25cm x 21.1mm, ~ 72.5 grams of packing, 100 angstrom in pore size. loading is 288-1,152 mg/ injection.

82 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Quick Scheme Method Development FOR THE REGIS PIRKLE-TYPE CHIRAL STATIONARY PHASES

STEP 1: STEP 3: Choosing the Appropriate Column: Start with a high percentage (~50%) of strong solvent (ethanol, IPA, ect.): We recommend using the following sequence of columns to start your method development. When doing method development at Starting with a strong solvent system ensures that all peaks will Regis, the Whelk-O is our first choice as it exhibits the broadest elute off the column quickly. degree of generality.

Order of Preference: Whelk-O ULMO Sample: Naproxen DACH-DNB Column: (R,R)-Whelk-O 1 25 cm x 4.6 mm α-Burke Mobile Phase: (50/50) Hexane/Ethanol β-Gem Flow Rate: 1.5 mL/min Pirkle 1-J Detection: UV 254 nm Run Time: 6.5 min Leucine Phenylglycine

STEP 2: Choosing the Mobile Phase:

Certain factors such as solubility and future considerations for preparative work usually help to determine whether to perform If you achieve any resolution, (such as the above sample) you method development with reversed-phase or normal phase solvents. Pirkle-Type phases can be used in both modes, but move on to STEP 4. typically performs the best with normal phase solvents. Since the If your sample comes off in the void, decrease the strong majority of analytical Chiral methods move on to preparative solvent by half. separations, we recommend using normal phase solvents. If your sample is now out of the void and you have Typical Mobile Phase Combinations: resolution, move on to STEP 4. Hexane/IPA Heptane/IPA If your sample is out of the void, and there is no resolution, Hexane/Ethanol Methanol/H2O change the column. Hexane/CH2CL2/Ethanol Ethanol/H2O Hexane/Ethyl Acetate Acetonitrile/H2O Heptane/Ethanol Methanol/CH2CL2 Heptane/CH2CL2 THF/H2O Hexane/CH2CL2 Ethanol/CH2CL2

Steps 4 and 5 continued on pages 84 & 85

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 83 Quick Scheme Method Development FOR THE REGIS PIRKLE-TYPE CHIRAL STATIONARY PHASES

STEP 4: Add a Mobile Phase Modifier (usually ~ 0.1%)

As you can see, the peak shape of the initial separation is very poor. To rectify this problem, a modifier is usually added. If you are satisfied with the peak shape—you do not need to add a modifier—move on to STEP 5 and optimize your separation.

For basic or amine groups—add triethylamine, diethylamine or ammonium acetate For acidic groups—add acetic acid, trifluoroacetic acid or ammonium acetate

Although resolution increased with the addition of 0.1% Resolution and peak shape are excellent with the addition of of triethylamine to the mobile phase, the peak shape is still 0.1% of acetic acid very poor. Try adding a different modifier

Recapping The First Four Steps:

For this sample, you can stop at 50/50 Hexane/Ethanol + 0.1% acetic acid if you are only looking for a basic method or you can carry it forward to STEP 5 and optimize.

84 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ Quick Scheme Method Development FOR THE REGIS PIRKLE-TYPE CHIRAL STATIONARY PHASES

STEP 5: Optimizing your method:

Optimizing a Chiral method is very similar to optimizing an achiral method. Changing mobile phase component concentrations and even the components themselves can dramatically change resolution.

Increase the concentration of the weaker solvent:

Increasing the hexane content increased the resolution in this example. Again, you can stop here and accept this as optimized or continue on.

Change the strong solvent:

By substituting IPA for ethanol, an increase in both resolution and alpha were achieved.

Optimization of a Chiral method can be as simple or as complicated as you want it to be. Different mobile phase components can be used; modifiers can be changed or eliminated; you can switch to reversed-phase solvents; you can change columns. The possibilities are endless. We suggest you keep it as simple as possible. Once you have achieved an acceptable separation, move on to the next project. Small increases in resolution and alpha are usually not worth the time spent in method development to achieve those increases.

Not sure which chiral column to use for your separation?

Let the professional staff at Regis assist you with its free chiral screening service. Simply fill out the chiral screening data sheet (see page 91 of this Guide) and pre-fax it to Regis or send it along with your sample of interest. [email protected] STRICTLY CONFIDENTIAL • FAST TURN AROUND TIME • NO OBLIGATION TO THE CUSTOMER REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral?85 REFERENCES 1. Pirkle, W. H.; Welch, C. J.; Burke, J. A., Lamm, B., Target-directed Design of 26. Welch, C.J.; Perrin, S.R., The Whelk-O 1 Chiral Stationary Phase: Some Recent Chiral Stationary Phases, Analytical Proceedings, 1992, 29, 225. Developments, Poster presented at the 4th International Symposium on Chiral 2. Pirkle, W. H.; Welch, C. J.; Hyun, M. H., Concerning the Role of Face-to-Edge Discrimination, Sept. 22, 1993, Montréal. π-π Interactions in Chiral Recognition, J. Chromatogr., 1992, 607, 126. 27. Stringham, R.W., Relationship Between Resolution and Analysis Time in Chiral 3. Pirkle, W. H.; Welch, C. J.; Lamm, B., Design, Synthesis, and Evaluation of an Subcritical Fluid Chromatography, Chirality, 1996, 8, 249-257. Improved Enantioselective Naproxen Selector, J. Org. Chem., 1992, 57, 3854. 28. Courtesy of Suzanne Leung, Department of Pharmaceutics, University of 4. Pirkle, W. H.; Welch, C. J., An Improved Chiral Stationary Phase for the Minnesota. Chromatographic Separation of Underivatized Naproxen Enantiomers, J. Liq. 29. Courtesy of Dhimant Desai, American Health Foundation. Chromatogr., 1992, 15(11), 1947. 30. Courtesy of Hal Butler, Sepracor, Inc. 5. Pirkle, W. H.; Welch, C. J.; Wilson, S. R., Assignment of Absolute Configuration 31. Courtesy of Allan Rettie, Department of Medicinal Chemistry, University of to an Improved Enantioselective Naproxen Selector, Chirality, 1994, 6, 615. Washington. 6. Welch, C. J., Analytical & Semipreparative Separation of Enantiomers Using the 32. Courtesy of Chet Mathis, Department of Radiology, University of Pittsburgh Whelk-O 1 Chiral Stationary Phase: Naproxen & Abscisic Acid as Case Studies, School of Medicine. Chemistry in New Zealand, 1993, July, 9. 33. Welch, C.J.; Perrin. S.R., Improved Chiral Stationary Phase for ß-blocker 7. Pirkle, W. H.; Welch, C. J., Use of Simultaneous Face to Face to Edge Enantioseparations, J. Chromatogr., 1995, 690, 218. π π - Interactions to Facilitate Chiral Recognition, Tetrahedron: Asymmetry, 1994, 34. Pirkle, W.H.; Burke, J.A., Preparation of a Chiral Stationary Phase from an 5, 777. α-amino Phosphonate, Chirality, 1989, 1, 57. 8. Wilson, S. R.; Wu, Y.; Kaprinidis, N. A.; Schuster, D. I.; Welch, C. J., Resolution 35. Pirkle, W.H.; Burke, J.A., Chiral Stationary Phase Designed for β-blockers, of Enantiomers of C60-Enone Photoadducts: Mirror Image Fullerenes, J. Org. J. Chromatogr., 1991, 557, 173,. Chem., 1993, 58, 6548. 36. Perrin, S.R., “Fast Liquid Chromatography for the Analysis of Enantiomers” In 9. Welch, C. J., An Improved Method for the Direct Chromatographic Resolution of Pharmaceutical and Biomedical Applications of Liquid Chromatography; Riley, Abscisic Acid Enantiomers, Chirality, 1993, 5, 569. M., Lough, W.J., Wainer, Eds.; Pergamon Division of Elsevier Science Ltd.: 10. Pirkle, W. H.; Welch, C. J.; Zych, A. J., Chromatographic Investigation of the Oxford, 1994; Vol. 1, Chapter 3. Slowly Interconverting Atropisomers of Hindered Naphthamides, J. Chromatogr., 37. Courtesy of Les Dolak, Department of Chemical & Biological Screening, 1993, 648,101. Pharmacia & Upjohn, Inc. 11. Zhen, L.; Conser, K. R.; Jacobsen, E. N., Asymmetric Alkene Aziridination with 38. Pirkle, W.H.; Gan, K.Z.; Brice, L.J., The Enhancement of Enantioselectivity by Readily Available Chiral Diimine-Based Catalysts, J. Amer. Chem. Soc., 1993, Halogen Substitutes, Tetrahedron: Asymmetry, 1996, 7, 2813-2816. 115, 5326. 39. Pirkle, W.H.; Gan, K.Z., in press, 1997. 12. Blum, A. M.; Lynam, K. G.; Nicolas, E. C., Use of a New Pirkle-type Chiral 40. Pirkle, W.H.; Brice, L.J.; Caccamese, S.; Principato, G.; Failla, S., Stationary Phase in Analytical and Preparative Subcritical Fluid Chromatography J. Chromatogr., 1996, 721, 241-246. of Pharmaceutical Compounds, Chirality, 1994, 6, 302. 41. Pirkle, W.H.; Koscho, M.E.; Wu, Z., High-Performance Liquid Chromatographic 13. Zhang, Y.; Schuster, G. B. A Search for Photoresolvable Mesogens: Synthesis and Separation of the Enantiomers of N-Aryloxazolinones, N-aryl Thiazolinones and Properties of a Series of Liquid Crystalline, Axially Chiral 1-Benzylidene-4 - their Sulfur Derivatives on a Synthetic Chiral Stationary Phase, J. Chromatogr., [4'-[(p - alkylphenyl)ethnyl]phenyl]cyclohexanes, J. Org. Chem., 1994, 59, 1855. 1996, 726, 91-97. 14. Pirkle, W. H.; Welch, C. J., Chromtographic and 1H NMR support for a 42. Pirkle, W.H.; Koscho, M.E., J. Chrom, in press, 1997. proposed chiral recognition model, J. Chromatogr., 1994, 683, 347. 43. Szczerba & Welch, Regis Technologies, Inc., unpublished results. 15. Wan, K. T.; Davis, M. E., Asymmetric Synthesis of Naproxen by Supported Aqueous-Phase Catalysis, Journal of Catalysis, 1994, 148, 1. 44. Caccamese, S., Tetrahedron: Asymetry, 1996, 7, 2577-2584. 16. Cardellina, J.H.; Bokesch, H.R.; McKee, J.C.; Boyd, M.R., Resolution and 45. Kennedy, J.K., Comparison of Chiral Separations on Polysaccharide Chiral Comparative Anti-HIV Evaluation of the Enantiomers of Calanolides A and B, Stationary Phases to an Improved Pirkle Phase, J. Chromatogr., 1996, 725, Bioorg & Med. Chem. Lett., 1995, 1011. 219-224. 17. Rychnovsky, Pettit & Welch, unpublished results. 46. Szczerba, T. J., Regis Technologies, Inc., unpublished results. 18. Welch, Szczerba & Perrin, Regis Technologies, Inc., unpublished results. 47. Uray, G.; Kosjek, B., Simultaneous Enantioseparation of Flobufen and its Diastereomeric Metabolites on a Pirkle Type Chiral Stationary Phase, Poster 19. Pickard, S.T.; Pirkle, W.H.; Tabatabai, M.; Vogt, W.; Boehmer, V., Dissymmetric presented at the 11th International Symposium on Chiral Discrimination, Calix[4]arenes: Optical Resolution of Some Conformationally Fixed Derivatives, July 25, 1999, Chicago. Chirality, 1993, 5, 310. 48. Courtesy of Georg Uray, Karl Franzens University, Austria; Norbert Maier, 20. Villani, C.; Pirkle, W.H., Direct High-Performance Liquid Chromatographic University of Vienna, Austria; Wolfgang Lindner, University of Vienna, Austria. Resolution of Planar Chiral Tricarbonyl (h6-arene)-chromium(0) Complexes, J. Chromatogr., 1995, 693, 63. 49. Pirkle, W.H.; Lee, W.; Welch, C.J., Enantiomer, 1997, 2, 423-431. 21. Villani, C.; Pirkle, W.H., Chromatographic Resolution of the Interconverting 50. Pirkle, W.H.; Lee, W., Bull. Kor. Chem. Soc., 1998, 19(11), 1277-1280. Stereoisomers of Hindered Sulfinyl and Sulfonyl Naphthalene Derivatives, 51. Lee, W., Bull. Kor. Chem. Soc., 1998, 19(7), 715-717. Tetrahedron: Asymmetry, 1995, 6, 27-30. 52. Hyun, M.H.; Jin, J.S.; Lee, W., Bull. Kor. Chem. Soc., 1997, 18(3), 336-339. 22. Casarini, D.; Lunazzi, L.; Alcaro, S.; Gasparrini, F.; Villani, C., Atropisomerism in 53. Kim, S.W.; Ahn, S.Y.; Koh, J.S.; Lee, J.H.; and Cho, H.Y., Tetrahedron Letters, Hindered Naphthyl Sulfones Investigated by Dynamic NMR and Dynamic HPLC 1997, 38(26), 4603-4606. Techniques, J. Org. Chem., 1995, 60, 5515. 54. Lee, W.; Kim, B.H, J. Of High Resolution Chromatogr., 1998, 21(3), 189-192. 23. Hamper, B.C.; Dukesherer, D.R.; Moedritzer, K., Analytical and Preparative 55. Courtesy of Wonjae Lee, LG Chemicals, Korea. Separation of the Enantiomers of Pyrazole Phenyle Ether Herbicides on Three 56. Lee, J.Y.; Lee, Y.S.; Chung, B.Y.; Park, H., Tetrahedron, 1997, 53(7), 2449- Chiral Stationary Phases., J. Chrom., 1994, 666, 479-484. 2458. 24. Suarez, M.; Schuster, G.B., Photoresolution of an Axially Chiral 57. Lee Wonjae, Analytical Lett., 1997, 30(15), 2791-2799. Bicyclo[3.3.0]octan-3-one: Phototriggers for a Liquid-Crystal-Based Optical Switch, J. Amer. Chem. Soc., 1995, 117, 6732. 58. K. Gyimesi-Forras, Gy. Szasz, M. Szabo and J. Kokosi: Chiral liquid chromatographic separation of new potential cholecystokinin antagonist nitrogen- 25. Lalonde, J.J.; Govardhan, C.; Khalaf, N.; Martinez, A.G.; Visuri, K.; Margolin, containing heterocycles, Poster presented at the 12th International Symposium on A.L., Cross-linked Crystals of Candida Rugosa Lipase: Highly Effiecient Catalyst Chiral Discrimination, Sept. 24, 2000, Chamonix. for the Resolution of Chiral Esters, J. Amer. Chem. Soc., 1995, 117, 6845. 59. Courtesy of Dr. Francesco Gasparrini, Misiti,Villani, et al,; Rome University “La Sapienza.” 60. Courtesy of Georg Uray, Karl Franzens University, Austria.

NOTES If you have published literature or intend to publish literature referencing any of Regis’ columns (Pirkle-types or others), we would appreciate a copy for our 8210 Austin Avenue files. Please send it directly to Regis (address at right). Morton Grove, IL 60053 USA Regis would appreciate the opportunity of obtaining your permission to tel: 847 967-6000 800 323-8144 reference your material in our Application Guides. Please let us know if you fax: 847 967-1214 have application information you would like included in our future guides. [email protected] PLEASE CONTACT REGIS FOR MORE INFORMATION. website: www.registech.com 86 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ INDEX OF APPLICATION BY COMPOUND

Aryl Propionic Acid Non Steroidal Basic Amine ...... 15 1-(o-Chlorophenyl) Ethanol...... 31 Nimodipine ...... 46 Anti-Inflammatory Drugs Trans-11,12-Diamino- 1-(o-Methoxyphenyl) Ethanol.....29 Sulfone Atropisomer ...... 41 (NSAIDS)...... 8-11 9,10-dihydro-9,10- 1-(o-Methylphenyl) Ethanol...... 30 Sulfoxide Atropisomer...... 41 α-Trityl-2-naphthalene ethanoanthracene ...... 15 1-(p-Bromophenyl) Ethanol...... 30 Vapol...... 46 Propionic Acid...... 10 1-(p-Fluorophenyl) Ethanol ...... 30 2-(4-Hydroxy-Phenoxy) Basic Nitrogen ...... 15 1-(p-Chlorophenyl) Ethanol ...... 31 Optical Switches, Liquid Propionic Acid...... 10 Troger’s Base...... 15 1-(p-Methylphenyl) Ethanol...... 29 Crystal Components, etc...... 47 3,5-Dimethylanilide-R,S- 1-Phenylpentanol ...... 27 Mesogens...... 47 Ibuprofen ...... 10 Esters, Lactones, Ketones, 1-Phenyl-2-propanol ...... 29 Phototriggers...... 47 Carprofen...... 11 Anhydrides ...... 16-19 2-Methoxyphenyl Phenyl Cicloprofen...... 8,9 1’-Acetoxychavicol Acetate...... 19 Carbinol ...... 28 Allenes ...... 48-52 Etodolac...... 8 1,3,5-Triphenylpent-4-yn-1-one ..18 2-Naphthyl-2-Butanol ...... 26 Fenoprofen ...... 8 2-Methyl-1-Indanone ...... 16 2-Thiopheneethanol ...... 29 Organometallic Compounds ...53-55 Flurbiprofen ...... 9 2-Methyl-1-Tetralone...... 18 3-Thiopheneethanol ...... 29 Hydratropic Acid...... 11 3-Methyl-1-Indanone ...... 17 9-Anthryl Trifluoromethyl Agricultural Compounds ...... 56-60 Ibuprofen...... 9 Buckminsterfullerene-Enone Carbinol ...... 25 Bromacil...... 56 Indoprofen...... 10 [2+2] Photoadducts...... 19 9-Anthrylethanol ...... 26 Chlorflurecol Methyl ...... 58 Ketoprofen...... 8 Diperodon ...... 18 Acenaphthenol...... 25 Chrysanthemic Acid- Ketoprofen as 1-naphthylamide...8 DPHB...... 17 Ibuprofenol ...... 25 Ethyl Ester ...... 57 Loxoprofen ...... 9 Ethyl-2-(p-Hydroxyphenoxy) Methyl 3-Phenyl-3azido- Cis:trans Cypermethrin...... 59 Naproxen (normal phase) .....9,10 Propionate ...... 19 2hydroxypropanoate Crotoxyphos ...... 58 Naproxen (reversed phase) ...... 9 Methyl Mandelate ...... 16 (Erythro-diastereomer) ...... 29 Devrinol, Napropamide ...... 58 Naproxen (semi prep)...... 8 Tert-butyl-2(benzamido) Phenyl Cyclohexyl Carbinol...... 28 Diclofop Methyl...... 58 Naproxen Diisopropyl Amide .....9 cyclopentyl carbamate...... 19 Phenyl Ethyl Carbinol...... 27 Dinocap ...... 60 Naproxen Dimethyl Amide ...... 10 Phenylethylene Glycol ...... 31 Fenvalerate...... 60 Naproxen Methyl Amide...... 10 Amides, Imides, Phenyl Isopropyl Carbinol ...... 28 Fenoxaprop-ethyl...... 60 Naproxen Methyl Ester ...... 10 Carbamates, etc...... 20-24 Phenyl Methyl Carbinol...... 27 Fluazifop-butyl...... 60 Pirprofen ...... 8 β-Lactam...... 24 Phenyl Phenylethyl Carbinol...... 28 Haloxyfop-ethoxyethyl...... 60 Rebamipide ...... 10 BOC-Ala ...... 20 Phenyl Propyl Carbinol...... 27 Leptophos, Phosvel ...... 57 Tiaprofenic Acid...... 8 CBZ Nornicotine ...... 20 Phenyl Tribromomethyl Mecoprop ...... 57 CBZ-Phe ...... 20 Carbinol ...... 27 Mecoprop Methyl ...... 56 Other Carboxylic Acids ...... 11-15 CBZ-Val...... 20 Propafenone ...... 28 Metalaxyl ...... 57 α-Methoxyphenyl Acetic Acid ...13 Cyclopentyl Benzoyl-diamide ....24 Ranolazine ...... 31 Metolachlor ...... 57 1,1’-Binaphthyl-2,2’- EEDQ ...... 20 Terfenedine...... 28 Omite ...... 57 Diylhydrogen Phosphate ...... 12 Tert Butyl Phenyl Carbinol ...... 25 Permethrin ...... 56 1-Cyclohexyl-1-phenylacetic Epoxides...... 24 Tetrahydrobenzopyrene-7-ol .....26 PPO Inhibitors ...... 56,58,59 Acid ...... 14 m-Cl-Styrene Oxide...... 24 Trans Phenyl Cyclohexanol Propiconazole, Tilt...... 58 1-Cyclopentyl-1-phenylacetic Stilbene Oxide...... 24 (Analytical vs. Quizalofop-ethyl...... 60 Acid ...... 14 Styrene Oxide...... 24 Preparative Run) ...... 28 Resmethrin...... 57 2-(2-Chloro-4-methylphenoxy) Sethoxydim...... 57 Propionic Acid...... 14 Alcohols...... 25-31 Diols, Hydroxyketones, etc...... 32 Silvex Methyl ...... 59 2-(3-Chlorophenoxy) α-Naphthyl Methyl Carbinol .....25 Anisoin ...... 32 Tetramethrin...... 56 Propionic Acid...... 14 β-Naphthyl Methyl Carbinol .....26 Benzoin...... 32 Tetramisole ...... 59 2-Phenylcyclopropane 1,1’-Bi-2-Naphthol ...... 26 Hydrobenzoin...... 32 Carboxylate ...... 12 1,1’-Binaphthol Ipsdienol ...... 32 Miscellaneous Pharmaceuticals61-73 2,3-Dibenzoyl-Tartaric Acid ...... 15 Monomethylether ...... 28 Alfuzosin ...... 72 4-Chloromandelic Acid ...... 13 1,1,2,-Triphenyl-1, Sulfoxides...... 33-35 Althiazide...... 71 4-(Trifluoromethyl)- 2-Ethanediol ...... 27 Omeprazole ...... 34 Bendroflumethiazide ...... 61,67 Mandelic Acid...... 15 1,2,3,4-Tetrahydro-1-Naphtol ...25 Pantoprazole ...... 35 Bupivacaine...... 62 Calcium Channel Blocker ...... 12 1-(4-Benzyloxy) Phenyl Ethanol..30 Sulfinpyrazone...... 34 Chlormezanone...... 72 Ditoluoyltartaric Acid ...... 14 1-(4-Hydroxyphenyl) Ethanol.....29 Chlorthalidone ...... 68 Ketorolac...... 13 1-(4-Methoxyphenyl)- Phosphorous Compounds ...... 36-38 Clenbuterol...... 71 Mandelic Acid ...... 12 2-butanol ...... 29 Cyclophosphamide...... 36 Coumachlor...... 69 Phenylbutyric Acid...... 11 1-(4-Methoxyphenyl)- Phosphine Selenium Oxide ...... 37 Cromakalim...... 70 Phenylsuccinic Acid ...... 13 2-propanol ...... 29 Secondary Phosphine Cyclandelate ...... 62 Suprofen ...... 14 1-[(4-Phenyl) Phenyl] Ethanol.....30 Oxide...... 37,38 Cyclothiazide...... 61 Tetrahydropyrimidine 1-(m-Chlorophenyl) Ethanol...... 31 Tertiary Phosphine Oxide ....37,38 Dexmedetomidine...... 68 Carboxylic Acid...... 11 1-(m-Methylphenyl) Ethanol ...... 30 Dihydrotetrabenazine ...... 72 Trolox ...... 12 1-(m-Trifluoromethylphenyl) Atropisomers ...... 39-46 Doxazosin ...... 72 Trolox-methylether ...... 14 Ethanol ...... 30 Adam’s Acid Diethylamide ...... 46 Ethotoin...... 71 Vanilmandelic Acid ...... 14 1-Naphthyl-2-Butanol ...... 26 Amlodipine...... 46 Flobufen ...... 68 Index of Application by Compound continued on page 88

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 87 INDEX OF APPLICATION BY COMPOUND continued from page 87

Flobufen Metabolites...... 68 2-cis-4-trans-Abscisic Acid...... 75 Fluridil...... 72 2-trans-4-trans-Abscisic Acid...... 75 Hanessian’s Lignan ...... 63 Abscisic Acid...... 76 Idazoxan...... 73 Abscisic Acid Methyl Ester...... 75 Ifenprodil...... 69 Calanolide A ...... 75 Indapamide ...... 62,67 Combretastatin D-1...... 75 Isoxsuprine ...... 70 Flavanone ...... 75 Isradipine (normal phase)...... 63 Luciferin ...... 76 Isradipine (reversed phase)...... 63 Taxifolin ...... 76 Ketamine...... 69 Tetrahydropalmatine ...... 76 Ketoconazole...... 69 Lansoprazole ...... 71 ß-Blockers...... 76-78 Lorazepam ...... 71 Alprenolol ...... 77 Lorglumide...... 73 Atenolol ...... 77 McN 5652...... 62 Bambuterol ...... 76 Mephenytoin...... 61 Betaxolol ...... 77 Metolazone ...... 71 Bufuralol...... 77 Methadone Hydrochloride...... 71 Bupranolol...... 77 Modafinil ...... 73 Carazolol ...... 78 Mosapride...... 73 Metoprolol...... 77 Nadifloxacin...... 73 Nadolol ...... 78 Nicardipine ...... 63 Oxprenolol ...... 78 Nirvanol...... 61 Pindolol...... 78 Ofloxacin ...... 70 Practolol...... 78 Oxazepam ...... 61 Pronethalol ...... 78 p-Chloro-Warfarin ...... 62 Propranolol...... 78 Pantoprazole ...... 35 Timolol Maleate ...... 78 Pazufloxacin ...... 72 Tulobuterol HCL...... 77 Prilocaine ...... 70 Proglumide ...... 64 Amino Acids ...... 79-81 Quinazolone Derivatives .....68,69 1-Aminoindan ...... 79 SC 41930...... 63 1,2,3,4-Tetrahydro-1- Sulindac...... 73 naphthylamine ...... 79 Sulpiride ...... 69 4-Fluorophenylalanine...... 79 Temazepam...... 64,70 Arginine...... 79 Tetrabenazine...... 72 DOPA ...... 81 Thalidomide...... 61,67 Ethionine ...... 81 Tofisopam and it’s Glutamic Acid...... 81 Conformers ...... 69 Glutamine ...... 80 Tolperisone...... 62 Histidine...... 81 Trans-U-50488H...... 72 p-Hydroxy-Phenylglycine...... 80 Trichlormethiazide ...... 70 Kynurenine ...... 80 Troglitazone ...... 64 Leucine...... 79 Tropicamide ...... 63 Lysine...... 81 U-100057 ...... 63 Methionine ...... 79 U-94863 (analytical) ...... 64 Norleucine ...... 79 U-94863 (preparative)...... 63 Norvaline...... 80 Warfarin (normal phase).....68,70 Phenylalanine ...... 80 Warfarin (reversed phase)...... 70 Phenylglycine...... 80 Zopiclone ...... 71 Serine ...... 80 Tryptophan ...... 80 Barbiturates ...... 74 Tyrosine ...... 79 Hexobarbital...... 74

Ureas...... 74 1-Naphthylureaphenethylamine.74

Diol Epoxides ...... 74 r-7,t-8-Dihydroxy-t-9,10-epoxy- 7,8,9,10-tetrahydrobenzo [a]pyrene ...... 73

Natural Products ...... 75-76 88 REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ INDEX OF APPLICATION BY COLUMN TYPE

α-Burke ...... 2 ß-GEM 1 1-(p-Chlorophenyl) Ethanol...... 31 Whelk-O 1 and 2 Alprenolol...... 77 r-7,t-8-Dihydroxy-t-9,10-epoxy- 1-(p-Fluorophenyl) Ethanol...... 30 α-Methoxyphenyl Acetic Atenolol...... 77 7,8,9,10-tetrahydrobenzo 1-(p-Methylphenyl) Ethanol...... 30 Acid...... 13 Bambuterol ...... 76 [a]pyrene ...... 74 1-Phenylpentanol ...... 27 1’-Acetoxychavicol Acetate ...... 19 Betaxolol ...... 77 Tofisopam and it’s Conformers.69 1-Phenyl-2-propanol ...... 29 1,1’-Binaphthyl-2,2’- Carazolol ...... 78 2-(2-Chloro-4-methylphenoxy) Diylhydrogen Phosphate...... 12 Clenbuterol ...... 71 Leucine Propionic Acid ...... 14 2-(3-Chlorophenoxy) Diperodon ...... 18 Hexobarbital...... 74 2-(4-Hydroxy-Phenoxy) Propionic Acid ...... 14 Lansoprazole...... 71 Luciferin...... 76 Propionic Acid ...... 10 2-cis-4-trans-Abscisic Acid ...... 75 Methadone Hydrochloride ...... 71 2-Methoxyphenyl Phenyl 2-Methyl-1-Indanone...... 16 Metoprolol ...... 77 Phenylglycine Carbinol...... 28 2-Methyl-1-Tetralone...... 18 Omeprazole ...... 34 1-Naphthylureaphenethylamine 74 2-Naphthyl-2-Butanol...... 26 2-Phenylcyclopropane Pantoprazole...... 35 2-Thiopheneethanol...... 29 Carboxylate...... 12 Practolol ...... 78 Pirkle 1-J 2,3-Dibenzoyl-Tartaric Acid .....15 2-trans-4-trans-Abscisic Acid.....75 Pronethalol...... 78 3,5-Dimethylanalide-R,S- 3-Thiopheneethanol...... 29 3-Methyl-1-Indanone...... 17 Tulobuterol HCL...... 77 Ibuprofen...... 10 9-Anthryl Trifluoromethyl 4-Chloromandelic Acid...... 13 Adam’s Acid Diethylamide ...... 46 Carbinol...... 25 4-(Trifluoromethyl)- ChiroSil® RCA(+) and SCA(-) Bufuralol...... 77 9-Anthrylethanol ...... 26 Mandelic Acid ...... 15 1-Aminoindan ...... 79 Bupranolol ...... 77 Acenaphthenol ...... 25 Abscisic Acid ...... 76 1,2,3,4-Tetrahydro-1- Cis:trans Cypermethrin ...... 59 Althiazide...... 71 Abscisic Acid Methyl Ester...... 75 naphthylamine...... 79 Oxprenolol ...... 78 Bendroflumethiazide ...... 67 Alfuzosin ...... 72 4-Fluorophenylalanine ...... 79 Pindolol ...... 78 Calcium Channel Blocker...... 12 Amlodipine ...... 46 Arginine ...... 79 Propranolol ...... 78 Cyclothiazide...... 61 Anisoin...... 32 DOPA ...... 81 Timolol Maleate...... 78 Cyclopentyl Benzoyl-diamide ...24 Bendroflumethiazide ...... 61 Ethionine ...... 81 Trans-U-50488H...... 72 Ditoluoyltartaric Acid ...... 14 Benzoin...... 32 Glutamic Acid ...... 81 Etodolac ...... 8 BOC-Ala...... 20 Glutamine...... 80 ULMO Flobufen Metabolites...... 68 Bromacil ...... 56 Histidine ...... 81 α-Trityl-2-naphthalene Flobufen ...... 68 Buckminsterfullerene-Enone p-Hydroxy-Phenylglycine...... 80 Propionic Acid ...... 10 Indapamide ...... 67 [2+2] Photoadducts ...... 19 Leucine...... 79 α-Naphthyl Methyl Carbinol ....25 Ketoprofen as 1- Bupivacaine ...... 62 Lysine...... 81 β-Naphthyl Methyl Carbinol.....26 naphthylamide ...... 8 Calanolide A ...... 75 Methionine...... 79 1,1’-Bi-2-Naphthol ...... 26 Methyl 3-Phenyl-3azido- Carprofen...... 11 Norleucine...... 79 1,1’-Binaphthol 2-hydroxypropanoate CBZ nornicotine ...... 20 Norvaline ...... 80 Monomethylether...... 28 (Erythro-diastereomer) ...... 29 CBZ-Phe ...... 20 Phenylalanine...... 80 1,1,2,-Triphenyl-1,2- Naproxen...... 9 CBZ-Val...... 20 Phenylglycine ...... 80 Ethanediol ...... 27 Phenyl Cyclohexyl Carbinol .....28 Chlorflurecol Methyl...... 58 Serine ...... 80 1,2,3,4-Tetrahydro-1- Phenyl Ethyl Carbinol ...... 27 Chlormezanone...... 72 trans-11,12-Diamino-9,10- Naphtol ...... 25 Phenyl Isopropyl Carbinol...... 28 Chrysanthemic Acid- dihydro-9,10- 1,3,5-Triphenylpent-4-yn-1-one 18 Phenyl Methyl Carbinol ...... 27 Ethyl Ester...... 57 ethanoanthracene...... 15 1-Cyclohexyl-1- Phenyl Phenylethyl Carbinol .....28 Cicloprofen...... 8,9 Tryptophan ...... 80 phenylacetic Acid...... 14 Phenyl Propyl Carbinol...... 27 Combretastatin D-1 ...... 75 Tyrosine...... 79 1-Cyclopentyl-1- Phenyl Tribromomethyl Coumachlor ...... 69 phenylacetic Acid...... 14 Carbinol...... 27 Cromakalim ...... 70 DACH-DNB 1-(4-Benzyloxy) Phenyl Phenylbutyric Acid ...... 11 Crotoxyphos ...... 58 β-Blockers ...... 76,77 Ethanol...... 30 Phenylsuccinic Acid ...... 13 Cyclandelate...... 62 β-Lactam...... 24 1-(4-Hydroxyphenyl) Ethanol ....29 Prilocaine ...... 70 Cyclophosphamide ...... 37 Chlorthalidone ...... 68 1-(4-Methoxyphenyl)-2-butanol..29 Temazepam ...... 64 Devrinol, Napropamide...... 58 Fenoxaprop-ethyl ...... 60 1-(4-Methoxyphenyl)- Tert Butyl Phenyl Carbinol...... 25 Dexmedetomidine...... 68 Fluazifop-butyl ...... 60 2-propanol ...... 29 Tetrahydropyrimidine Diclofop Methyl ...... 58 Haloxyfop-ethoxyethyl ...... 60 1-[(4-Phenyl) Phenyl] Ethanol ....30 Carboxylic Acid ...... 11 Dihydrotetrabenazine...... 72 Phosphine Selenium Oxide ...... 37 1-(m-Chlorophenyl) Ethanol ...... 31 Thalidomide ...... 67 Dinocap ...... 60 Quizalofop-ethyl ...... 60 1-(m-Methylphenyl) Ethanol ...... 30 Trans Phenyl Cyclohexanol Doxazosin ...... 72 Secondary Phosphine 1-(m-Trifluoromethylphenyl) (Analytical vs. DPHB ...... 17 Oxide ...... 37,38 Ethanol...... 30 Preparative Run)...... 28 EEDQ...... 20 Sulfoxides ...... 34 1-Naphthyl-2-Butanol...... 26 Trichlormethiazide ...... 70 Ethotoin ...... 71 Sulpiride...... 69 1-(o-Chlorophenyl) Ethanol...... 31 Trolox...... 12 Ethyl-2-(p-Hydroxyphenoxy) Tertiary Phosphine Oxide ...37,38 1-(o-Methoxyphenyl) Ethanol ....29 Trolox-methylether ...... 14 Propionate...... 19 1-(o-Methylphenyl) Ethanol ...... 30 Vapol...... 46 Fenvalerate ...... 60 1-(p-Bromophenyl) Ethanol ...... 30 Warfarin ...... 68 Fenoprofen ...... 8

Index of Application by Column Type continued on page 90

REGIS TECHNOLOGIES CHIRAL APPLICATION GUIDE VI • WWW.REGISTECH.COM/chiral/ 89 INDEX OF APPLICATION BY COLUMN TYPE continued from page 89

Flavanone...... 75 Propiconazole, Tilt ...... 58 Flurbiprofen ...... 9 Quinazolone Derivatives ....68,69 Fluridil...... 72 Ranolazine...... 31 Hanessian’s Lignan ...... 63 Rebamipide ...... 10 Hydrobenzoin ...... 32 Resmethrin ...... 57 Hydratropic Acid...... 11 SC 41930 ...... 63 Ibuprofen...... 9 Sethoxydim ...... 57 Ibuprofenol ...... 25 Silvex Methyl ...... 59 Idazoxan ...... 73 Stilbene Oxide ...... 24 Ifenprodil...... 69 Styrene Oxide...... 24 Indapamide ...... 62 Sulfinpyrazone ...... 34 Indoprofen ...... 10 Sulfone Atropisomer...... 41 Ipsdienol...... 32 Sulfoxide Atropisomer ...... 41 Isoxsuprine...... 70 Sulindac ...... 73 Isradipine (normal phase) ...... 63 Suprofen...... 14 Isradipine (reversed phase) ...... 63 Taxifolin ...... 76 Ketamine ...... 69 Temazepam ...... 70 Ketoconazole ...... 69 Terfenadine...... 28 Ketoprofen...... 8 Tert-butyl-2(benzamido) Ketorolac...... 13 cyclopentyl carbamate ...... 19 Kynurenine...... 80 Tetrabenazine ...... 72 Leptophos, Phosvel...... 57 Tetrahydrobenzopyrene-7-ol.....26 Lorazepam...... 71 Tetrahydropalmatine ...... 76 Lorglumide...... 73 Tetramethrin ...... 56 Loxoprofen...... 9 Tetramisole ...... 59 Mandelic Acid ...... 12 Thalidomide ...... 61 m-Cl-Styrene Oxide ...... 24 Tiaprofenic Acid...... 8 McN 5652 ...... 62 Tolperisone ...... 62 Mecoprop...... 57 Troger’s Base ...... 15 Mecoprop Methyl ...... 56 Troglitazone...... 64 Mephenytoin...... 61 Trolox...... 12 Mesogens ...... 47 Tropicamide...... 63 Metalaxyl ...... 57 U-100057 ...... 63 Methyl Mandelate...... 16 U-94863 ...... 63,63 Metolachlor...... 57 Vanilmandelic Acid...... 14 Metolazone...... 71 Warfarin (normal phase) ...... 70 Modafinil...... 73 Warfarin (reversed phase)...... 70 Mosapride ...... 73 Zopiclone ...... 71 Nadifloxacin...... 73 Nadolol...... 78 Naproxen (normal phase).....9,10 Naproxen (reversed phase) ...... 9 Naproxen (semi prep) ...... 8 Naproxen Diisopropyl Amide ....9 Naproxen Dimethyl Amide ...... 10 Naproxen Methyl Amide ...... 10 Naproxen Methyl Ester...... 10 Nicardipine ...... 63 Nimodipine...... 46 Nirvanol ...... 61 Ofloxacin ...... 70 Omite...... 57 Oxazepam ...... 61 p-Chloro-Warfarin...... 62 Pazufloxacin ...... 72 Permethrin ...... 56 Phenylethylene Glycol ...... 31 Phototriggers...... 47 Pirprofen...... 8 PPO Inhibitors ...... 56,58,59 Proglumide ...... 64 Propafenone ...... 28

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