Efficient Carbohydrate Synthesis by Controlled Inversion Strategies
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STEREOSELECTIVE GLYCOSYLATIONS and SYNTHESIS of HYALURONAN BIOSYNTHESIS INHIBITORS by Gilbert Ochieng Wasonga a THESIS Submitted
STEREOSELECTIVE GLYCOSYLATIONS AND SYNTHESIS OF HYALURONAN BIOSYNTHESIS INHIBITORS By Gilbert Ochieng Wasonga A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE CHEMISTRY 2010 1 ABSTRACT STEREOSELECTIVE GLYCOSYLATIONS AND SYNTHESIS OF HYALURONAN SYNTHESIS INHIBITORS By Gilbert Ochieng Wasonga Stereochemical control is an important issue in carbohydrate synthesis. Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition. In this work, the effects of additives and reaction solvent on stereoselectivity was examined using donors without participating protective groups on 2-O. We have established that the stereoselectivity could be directed by reaction solvent. The trend of stereochemical dependence on reaction solvent was applicable to a variety of reactions including the selective formation of β-mannosides. In the second part, 3-MeO-GlcNAc is efficiently prepared using a furanose oxazoline intermediate which is well suited for large scale synthesis without the need for extensive column chromatography. In addition, we have developed a robust and rapid procedure for the synthesis of 3-F-GlcNAc derivative required for inhibition studies of hyaluronan biosynthesis. In the course of our synthesis, we have shown the expanded utility of Lattrell-Dax method for carbohydrate epimerization reactions. II ACKNOWLEDGMENTS I would like to thank my advisor Professor Xuefei Huang for his guidance and support that have been instrumental in my graduate studies. Along the way, I have had the opportunity to be mentored by Doctor Youlin Zeng who was a very helpful mentor at the beginning of my chemistry research experience and I will always be grateful to him. -
Chemical Science
Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Highly selective acylation of polyamines and aminoglycosides by 5-acyl-5-phenyl-1,5-dihydro- Cite this: Chem. Sci.,2017,8,7152 4H-pyrazol-4-ones† Kostiantyn O. Marichev, Estevan C. Garcia, Kartick C. Bhowmick, Daniel J. Wherritt, Hadi Arman and Michael P. Doyle * 5-Acyl-5-phenyl-1,5-dihydro-4H-pyrazol-4-ones, accessible from arylpropargyl phenyldiazoacetates, are highly selective acyl transfer reagents for di- and polyamines, as well as aminoalcohols and aminothiols. As reagents with a carbon-based leaving group, they have been applied for benzoyl transfer with a broad selection of substrates containing aliphatic amino in combination with other competing nucleophilic Received 20th July 2017 functional groups. The substrate scope and levels of selectivity for direct benzoyl transfer exceed those Accepted 29th August 2017 of known benzoylating reagents. With exceptional selectivity for acylation between primary amines DOI: 10.1039/c7sc03184j bound to primary and secondary carbons, these new reagents have been used in direct site-selective Creative Commons Attribution 3.0 Unported Licence. rsc.li/chemical-science monobenzoylation of aminoglycoside antibiotics. Introduction 1-position of 1,2-diaminopropane,14d selective acylation of primary amines whose carbon attachment is primary, The formation of an amide bond by acyl transfer is a classic secondary or tertiary, has received scant attention.15 chemical reaction1 that has been extensively studied2 and widely We have recently prepared a novel heterocyclic compound that applied.3 Over the years numerous acyl transfer agents have been appeared to have the potential of being a selective benzoyl transfer investigated; their activities have been dependent on the leaving reagent. -
215-216 HH W12-Notes-Ch 15
Chem 215 F12 Notes Notes – Dr. Masato Koreeda - Page 1 of 17. Date: October 5, 2012 Chapter 15: Carboxylic Acids and Their Derivatives and 21.3 B, C/21.5 A “Acyl-Transfer Reactions” I. Introduction Examples: note: R could be "H" R Z R O H R O R' ester O carboxylic acid O O an acyl group bonded to R X R S acid halide* R' an electronegative atom (Z) thioester O X = halogen O R' R, R', R": alkyl, alkenyl, alkynyl, R O R' R N or aryl group R" amide O O O acid anhydride one of or both of R' and R" * acid halides could be "H" R F R Cl R Br R I O O O O acid fluoride acid chloride acid bromide acid iodide R Z sp2 hybridized; trigonal planar making it relatively "uncrowded" O The electronegative O atom polarizes the C=O group, making the C=O carbon "electrophilic." Resonance contribution by Z δ * R Z R Z R Z R Z C C C C O O O δ O hybrid structure The basicity and size of Z determine how much this resonance structure contributes to the hybrid. * The more basic Z is, the more it donates its electron pair, and the more resonance structure * contributes to the hybrid. similar basicity O R' Cl OH OR' NR'R" Trends in basicity: O weakest increasing basiciy strongest base base Check the pKa values of the conjugate acids of these bases. Chem 215 F12 Notes Notes –Dr. Masato Koreeda - Page 2 of 17. -
RSC Advances
RSC Advances View Article Online REVIEW View Journal | View Issue Dual protection of amino functions involving Boc Ulf Ragnarsson*a and Leif Grehnb Cite this: RSC Advances, 2013, 3, 18691 Protecting groups play a pivotal role in the synthesis of multifunctional targets and as amino functions often occur in this context, issues related to their protection become prominent. Primary amines are Received 13th June 2013, unique because they can accommodate two such groups. This review highlights various aspects related to Accepted 16th July 2013 the synthesis, properties and applications of products containing one or two Boc-groups resulting from DOI: 10.1039/c3ra42956c dual protection of amines and amides. Attention is directed towards cases of facilitated cleavage due to www.rsc.org/advances mutual interaction between two protecting groups on the same nitrogen. 1 Introduction In retrospect it seems that outside the peptide field the break-through in the use of Boc came a bit later as judged When in a synthetic project there is a need to protect an amino from the first monographs devoted to protecting groups.3 function, its conversion to tert-butyl carbamate is nowadays Creative Commons Attribution 3.0 Unported Licence. More recently the preferences have changed and nowadays Boc generally the first option, because of the attractive properties of is ranked as ‘‘one of the most commonly used protective 1 the resulting so-called Boc-derivative. Boc-protection was intro- groups for amines’’.4 Other NH-compounds including various duced in the late fifties and was rapidly applied in the field of protected/acylated amines have also been substituted in this peptide synthesis. -
United States Patent Office
3,384,473 United States Patent Office Patented May 21, 1968 2 By direct condensation, there is obtained: 3,384,473 O R DERVATIVES OF N-PHENYL-N-BENZOYL UREAS AS HERBECDES Daniel Pilon, Lyon, and Pierre Poignant, Saint-Rambert R Ile-Barbe, France, assignors to Société dite: Pechiney 5 Progil, Paris, France No Drawing. Filed Oct. 23, 1964, Ser. No. 406,171 Claims priority, application France, Oct. 25, 1963, 951,808 Finally, the substituted urea is for example condensed 9 Claims. (C. 71-120) O with an aromatic acid chloride carrying the required sub Stituents; the condensation is effected with elimination of hydrochloric acid. ABSTRACT OF THE DISCLOSUIRE It is possible to run a benzene solution of the acid chlo ride, particularly benzoyl chloride, into a suspension of The growth of plants is controlled by using as a her the substituted urea in benzene and then to heat the said bicidal agent an N-phenyl-N-benzoyl urea in which at Suspension to boiling point for eliminating the hydracid. least one hydrogen on the second urea nitrogen is re It is more convenient to operate in the presence of an acid placed by at least one alkyl, alkoxy, alkenyl or alkynyl acceptor, such as dimethylamine, trimethylamine, triethyl group containing less than 5 carbon atoms. The benzoyl amine, morpholine or pyridine. group can be substituted by lower alkyl or alkoxy groups, 20 According to a preferred method of preparation, the halogen, nitro, or nitrile. acid acceptor is itself used as solvent of the reaction mass -managerman-ow by using a large excess with respect to the stoichiometric quantity. -
Synthesis of Carbohydrate Building Blocks Via Regioselective Uniform Protection/Deprotection Strategies
Organic & Biomolecular Chemistry Synthesis of carbohydrate building blocks via regioselective uniform protection/deprotection strategies Journal: Organic & Biomolecular Chemistry Manuscript ID OB-REV-03-2019-000573.R1 Article Type: Review Article Date Submitted by the 21-Apr-2019 Author: Complete List of Authors: Wang, Tinghua; University of Missouri - St. Louis, Deparment of Chemistry and Biochemistry Demchenko, Alexei; University of Missouri - St. Louis, Deparment of Chemistry and Biochemistry Page 1 of 14 Organic & Biomolecular Chemistry Synthesis of carbohydrate building blocks via regioselective uniform protection/deprotection strategies Tinghua Wang and Alexei V. Demchenko* Department of Chemistry and Biochemistry, University of Missouri – St. Louis, One University Boulevard, St. Louis, Missouri 63121, USA O Scope 1 HO O n R PO O n-1 R Scope 2 OH PO n R P = protecting group R = anomeric substituent Scope 1: sugar is uniformly protected leaving only one (or two) free hydroxyl; Scope 2: uniformly protected sugar is deprotected to liberate only one (or two) hydroxyl ABSTRACT: Discussed herein is the synthesis of partially protected carbohydrates by manipulating only one type of a protecting group for a given substrate. The first focus of this review is the uniform protection of the unprotected starting material in the way that only one (or two) hydroxyl groups remain unprotected. The second focus involves regioselective partial deprotection of uniformly protected compounds in the way that only one (or two) hydroxyl groups become liberated.. Contents challenges in carbohydrate chemistry.1-3 During sequencing of simple monosaccharides into larger oligomeric networks, 1. Introduction and basic considerations most of the functional groups need to be temporarily blocked 2. -
Α-Chlorinated Toluenes and Benzoyl Chloride
α-CHLORINATED TOLUENES AND BENZOYL CHLORIDE Data were last reviewed in IARC (1982) and the compounds were classified in IARC Monographs Supplement 7 (1987a). 1. Exposure Data Benzyl chloride 1.1 Chemical and physical data 1.1.1 Nomenclature Chem. Abstr. Serv. Reg. No.: 100-44-7 Chem. Abstr. Name: (Chloromethyl)benzene IUPAC Systematic Name: α-Chlorotoluene Synonyms: Chloromethyl benzene; chlorophenylmethane; α-tolyl chloride 1.1.2 Structural and molecular formulae and relative molecular mass CH2Cl C7H7Cl Relative molecular mass: 126.6 1.1.3 Chemical and physical properties of the pure substance From Lide (1997), unless otherwise specified (a) Description: Colourless liquid with a pungent odour (Lewis, 1993) (b) Boiling-point: 179°C (c) Melting-point: –45°C 20 (d) Density: d10 1.10 (e) Solubility: Insoluble in water; slightly soluble in carbon tetrachloride; miscible with chloroform, diethyl ether and ethanol (Budavari, 1996) (f) Vapour pressure: 133 Pa at 22°C; relative vapour density (air = 1), 4.36 (Ver- schueren, 1996) (g) Stability: Decomposes in hot water to benzyl alcohol (United States Environ- mental Protection Agency, 1980); decomposes rapidly when heated in the pre- sence of iron (Budavari, 1996); combustible (Lewis, 1993) (h) Reactivity: Undergoes reactions both at the side-chain containing the chlorine and at the aromatic ring (Gelfand, 1979) –453– 454 IARC MONOGRAPHS VOLUME 71 (i) Flash-point: 67°C (closed cup); 74°C (open cup) (Lin & Bieron, 1993) (j) Explosive limit: Lower, 1.1% by volume of air (Lin & Bieron, 1993) (k) Octanol/water partition coefficient (P): log P, 2.30 (Verschueren, 1996) (l) Conversion factor: mg/m3 = 5.18 × ppm 1.2 Production and use The chemical processes associated with the manufacture of chlorinated toluenes are summarized in Figure 1. -
We Utilized a Similar Approach with DEP-Chymotryp- Two of The
PROBING THE TOPOGRAPHY OF THE ACTIVE SITE OF a-CHYMOTRYPSIN BY BERNARD F. ERLANGER DEPARTMENT OF MICROBIOLOGY, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA UNIVERSITY Communicated by Erwin Chargaff, May 16, 1967 This paper is a report of a study of the topography of the active center of a- chymotrypsin. In particular, it will deal with that portion involved in sub- strate binding and with its position in space relative to the nucleophilic serine residue that is believed to function in the catalytic mechanism.1 Since an enzyme must accommodate a substrate, the simplest approach to an understanding of the topography of the former might be a study of the conformation of the latter. However, this is not feasible with chymotrypsin. A typical sub- strate of chymotrypsin is acetyl L-phenylalanine ethyl ester.1 There is much evi- dence linking the susceptibility of this substrate to the aromatic ring of the amino acid (though aromaticity is not necessary since cyclic hexahydro derivatives are also substrates)2 and to the acylamido portion of the molecule. Benzoylamido may substitute for acetylamido and, in fact, yields a somewhat better substrate (higher keat)3 in the case of acyl L-tyrosine amide. However, since all of the above substrates are flexible molecules and therefore able to assume many conformations, there is no way of knowing their conformation when bound to the active center of a-chymotrypsin. In our early studies we chose to use an approach based upon the experiments of Wilson with acetylcholinesterase.4 Acetylcholinesterase and chymotrypsin belong to the class of enzymes called serine esterases.1 All members of this class contain an unusually reactive serine residue which acts as a nucleophile in the catalytic mechanism. -
Nucleotide Sugars in Chemistry and Biology
molecules Review Nucleotide Sugars in Chemistry and Biology Satu Mikkola Department of Chemistry, University of Turku, 20014 Turku, Finland; satu.mikkola@utu.fi Academic Editor: David R. W. Hodgson Received: 15 November 2020; Accepted: 4 December 2020; Published: 6 December 2020 Abstract: Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates. They are involved in processes that are targets for drug development, and their analogs are potential inhibitors of these processes. Drug development requires efficient methods for the synthesis of oligosaccharides and nucleotide sugar building blocks as well as of modified structures as potential inhibitors. It requires also understanding the details of biological and chemical processes as well as the reactivity and reactions under different conditions. This article addresses all these issues by giving a broad overview on nucleotide sugars in biological and chemical reactions. As the background for the topic, glycosylation reactions in mammalian and bacterial cells are briefly discussed. In the following sections, structures and biosynthetic routes for nucleotide sugars, as well as the mechanisms of action of nucleotide sugar-utilizing enzymes, are discussed. Chemical topics include the reactivity and chemical synthesis methods. Finally, the enzymatic in vitro synthesis of nucleotide sugars and the utilization of enzyme cascades in the synthesis of nucleotide sugars and oligosaccharides are briefly discussed. Keywords: nucleotide sugar; glycosylation; glycoconjugate; mechanism; reactivity; synthesis; chemoenzymatic synthesis 1. Introduction Nucleotide sugars consist of a monosaccharide and a nucleoside mono- or diphosphate moiety. The term often refers specifically to structures where the nucleotide is attached to the anomeric carbon of the sugar component. -
Mechanistic Investigations Into the Application of Sulfoxides in Carbohydrate Synthesis
This is a repository copy of Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/93061/ Version: Accepted Version Article: Fascione, Martin Anthony orcid.org/0000-0002-0066-4419, Brabham, Robin and Turnbull, W. Bruce (2016) Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis. Chemistry - A European Journal. ISSN 1521-3765 https://doi.org/10.1002/chem.201503504 Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis Martin A. Fascione*,[a] Robin Brabham,[a] and W. Bruce Turnbull*[b] Abstract: The utility of sulfoxides in a diverse range of The use of thioglycoside donors has been widespread since transformations in the field of carbohydrate chemistry has seen their introduction by Ferrier.[6] The next substantial step forward rapid growth since the first introduction of a sulfoxide as a in the use of thioglycoside derivatives came from Kahne and co- glycosyl donor in 1989. -
Carbohydrate Synthesis and Study of Carbohydrate- Lectin Interactions Using QCM Biosensors and Microarray Technologies
Carbohydrate Synthesis and Study of Carbohydrate- Lectin Interactions Using QCM Biosensors and Microarray Technologies Zhichao Pei 裴志超 KTH Chemical Science and Engineering Doctoral Thesis Stockholm 2006 Akademisk avhandling som med tillstånd av Kungliga Tekniska Högskolan i Stockholm framlägges till offentlig granskning för avläggande av filosofie doktorsexamen i kemi med inriktning mot organisk kemi, fredagen den 1 Dec., kl 10.00 i sal D3, KTH, Lindstedtsvägen 5, Stockholm. Avhandlingen försvaras på engelska. Opponent är Professor Roland J. Pieters, Utrecht University, the Netherlands. 1 ISBN 91-7178-503-5 ISRN KTH/IOK/FR--06/106--SE ISSN 1100-7974 TRITA-IOK Forskningsrapport 2006:106 © Zhichao Pei Universitetsservice US AB, Stockholm 2 Carbohydrate Synthesis and Study of Carbohydrate-Lectin Interactions Using QCM Biosensors and Microarray Technologies Zhichao Pei, Organic Chemistry, KTH Chemical Science and Engineering, SE-10044 Stockholm, Sweden Dissertation for the degree of Doctor of Philosophy in Chemistry, 2006. Abstract Interactions between carbohydrates and proteins are increasingly being recognized as crucial in many biological processes, such as cellular adhesion and communication. In order to investigate the interactions of carbohydrates and proteins, the development of efficient analytic technologies, as well as novel strategies for the synthesis of carbohydrates, have to be explored. To date, several methods have been exploited to analyze interactions of carbohydrates and proteins, for example, biosensors, nuclear magnetic resonance (NMR); enzyme-linked immunosorbent assays (ELISA), X-ray crystallography and array technologies. This thesis describes the development of novel strategies for the synthesis of carbohydrates, as well as new efficient strategies to Quartz Crystal Microbalance- (QCM-) biosensors and carbohydrate microarrays technologies. -
Glycosylation of Amino Acids and Efficient Synthesis of Glycosphingolipids
Georgia State University ScholarWorks @ Georgia State University Chemistry Theses Department of Chemistry 8-11-2015 Glycosylation of Amino Acids and Efficient Synthesis of Glycosphingolipids Jonathan Wooten Georgia State University, [email protected] Follow this and additional works at: https://scholarworks.gsu.edu/chemistry_theses Recommended Citation Wooten, Jonathan, "Glycosylation of Amino Acids and Efficient Synthesis of Glycosphingolipids." Thesis, Georgia State University, 2015. https://scholarworks.gsu.edu/chemistry_theses/74 This Thesis is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Theses by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. GLYCOSYLATION OF AMINO ACIDS AND EFFICIENT SYNTHESIS OF GLYCOSPHINGOLIPIDS by JONATHAN VALENTINE WOOTEN Under the Direction of Peng George Wang, PhD ABSTRACT Glycoscience is an emerging field of science that focuses on the study of the structure, biosynthesis, biology, and evolution of saccharides (sugars). It covers a broad range of subjects including microwave-assisted synthesis as well as sphingolipid synthesis. In this field, knowledge is limited due to the complexity of carbohydrates and their derivatives. Therefore, it is all the more important that synthesis of these complex molecules occurs in order to fully understand their biological significance. The following report summarizes