DOCSLIB.ORG

Stereochemistry

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Chapter 6 Stereochemistry Is the study of the static and dynamic aspects of the three-dimensional shapes of molecules. 6.1 Stereogenicity and stereoisomerism 6.1.1 Basic concepts and terminology Constitutional isomers: molecules with same molecular formular but different connectivity between the atoms. e.g.) 1-bromo and 2-bromobutane Stereoisomers: molecules that have the same connectivity but differ in the arrangement of atoms in space. e.g) cis- and trans-2-butene 1. enantiomers: nonsuperimposable mirror images of each other 2. diastereomers: stereoisomers that are not enantiomers - conformational isomers: are interconvertible by rotations about single bonds - configurational isomers: stereochemical isomers including enantiomers and diastereomers. configuration: the relative position or order of arrangement of atoms in space which characterizes a particular stereoisomer. - chiral: any object that is nonsuperimposable with its mirror images - achiral: if an object is not chiral, it is achiral. A molecule is achiral if it is superimposable on its mirror image. A molecule which has a plane of symmetry, a center of symmetry or rotation-reflection symmetry is achiral. An axis of symmetry (C2 axis) -> achiral과관계없음 A molecule is achiral if it is superimposable on its mirror image. A molecule which has a plane of symmetry, a center of symmetry or rotation-reflection symmetry is achiral. (나중에 다시 설명) chiral C2 OH Br achiral O Br OH a plane of symmetry (σ, S1) Br achiral Br a center of symmetry (i, S2) meso: compounds that contain stereogenic centers but are nevertheless achiral. Classic terminology Optically active: refers to the ability of a collection of molecules to rotate plane polarized light - must have an excess of one enantiomer. Racemic mixture (or racemate): a 50:50 mixture of enantiomers and is not optically active. However, enantiomers that do not have dramatically different refractive indices would not result in measurable rotations. -> in this case, they are optically inactive even though they are chiral. 따라서 optically active란 말은 사용하지 않는 것이 좋음. Chiral center or chiral (asymmetric) carbon: an atom or specifically carbon, respectively, that has four different ligands attached. Chiral carbons exist in molecules that are neither asymmetric nor chiral. Many molecules can exist in enantiomeric forms without having a chiral center. 이 말도 사용하지 않는 것이 좋음. chiral center CO2H H OH H OH CO2H achiral compound More modern terminology Stereocenter (stereogenic center): use this term instead of chiral center, it is stereogenic center if the interchange of two ligands attached to it can produce a new stereoisomer. A non-stereogenic center is one in which exchange of any pair of ligands does not produce a stereoisomer. -> the term ‘stereogenic center’ is broader than the term ‘chiral center’. A CWXYZ center does not guarantee a chiral molecule. However, a CWXYZ group is always a stereogenic center. stereogenic center: 두개의 CO2H 치환기를 바꾸면 stereoisomers H OH 가 생긴다 H OH CO2H meso form Typically, a molecule with n stereogenic, tetracoordinate carbons will have 2n stereoisomers -2n-1 diastereomers that exist as a pair of enantiomers. Epimers: are diastereomers that differ in configuration at only one of the several stereogenic centers. Carbohydrates: α-and β-anomers도 epimers의 한 형태임. 6.1.2 Stereochemical descriptors R, S system (Cahn-Ingold-Prelog system) 1 2 1 2 R1 R2 R1 R2 4 R4 3 R4 4 R3 3 R3 R S rectus (right) sinister (left) higher atomic number: higher priority isotopes (the one with higher mass is assigned the higher priority) Tricoordinate -> stereogenic center phantom atom: the lowest priority H3C S CH3 CH2CH3 CH2CH3 high energy S CH3 H3C barrier R S phantom atom: the lowest priority P CH3 CH2CH=CH2 P CH3 CH2CH=CH2 high energy barrier R S E, Z system lower higher If an H atom is on each of the double bond, Opposite: E (entgegen) conventionally, cis and trans can be used. (cf) same: Z (zusammen) D, L system mainly used for amino acids and carbohydrates Fischer projection Horizontal lines: bonds coming out of the plane of the paper Vertical lines: bonds projecting behind the plane of the paper The most oxidized group: top CH2OH (carbohydrates) or R (amino acids): bottom D: dextro, right L: levo, left DD L D L Natural amino acids: L-amino acids Important point No direct relationship between the R/S and D/L and the sign of optical rotation of the molecule. Helical descriptors – M, P system Many chiral molecules lack a conventional center that can be described by R/s or E/Z. -> typically helical, propeller, screw-shaped structures -> a right-handed helix (clockwise): P (plus), a left handed helix (anti-clockwise): M (minus) H H CH3 Cl NO2 H3C NO2 CH3 CH3 H3C H H 6.1.3 Distinguishing enantiomers Chiral column chromatography Enantiomeric excess = (Xa – Xb) x 100, Xa: mole fraction of a, Xb: mole fraction of b High field NMR spectroscopy with chiral shift reagents NMR spectroscopy of derivatives that are diastereomeric Chromatography (HPLC and GC) with chiral stationary phases NMR spectroscopy of derivatives that are diastereomeric eclipsed eclipsed S OH R H R R 1 F C OMe S 2 H R R 3 H 1 2 R2 O Ph COCl R1 O or O OMe O OMe or (R)-MTPA-Cl F3C F3C methoxy trifluoromethyl R OH H phenylacetyl chloride R2 R1 (Mosher’s reagent) S: R1 -> upfield R: R2 -> upfield due to anisotropic effect of phenyl ring Methods: (R/S) racemate + (R)-MTPA-Cl 50 : 50 (R-R-MTPA : S-R-MTPA) OH, NH2, SH 등 R S ppm R, S peak 결정 sample + (R)-MTPA-Cl Derivatives R S ee 80% 90 10 OMe NH α-H L D D D L D D L D O D,L F3C S OCO2t-Bu N H Ph OMe OTBS > 98%ee NH α-H OMe L D D D L D D L D O D,L F3C S OCO2Bn N H Ph OMe Me Me > 98%ee Optical activity and chirality Optical activity: the ability of a sample to rotate a plane of polarized light. A rotation to the right: + or dextrorotatory (d) A rotation to the left: - or levorotatory (l) Optical activity establishes that a sample is chiral, but a lack of optical activity does not prove a lack of chirality. Optical activity (α) Specific optical activity [α] 25 [α]D -> sodium D line (589 nm emission line of sodium arc lamp) [α] mixture of enantiomer Optical purity (%) = x 100 [α] pure enantiomer 6.2 Symmetry and stereochemistry 6.2.1 Basic symmetry operations o Proper rotation (Cn) -> a rotation around an axis by (360/n) that has the net effect of leaving the position of the object unchanged. C2; 180 rotation, C3; 120 rotation o Improper symmetry (Sn) -> rotation and reflection; involves a rotation of (360/n) , combined with a reflection across a mirror plane that is perpendicular to the rotation axis. S1; just a mirror reflection (σ) S2; equivalent to a center of inversion (i) 90o 60o 180o 6.2.2 Chirality and symmetry A necessary and sufficient criterion for chirality is an absence of Sn axes; the existence of any Sn axis renders an object achiral. C2 Asymmetric is defined as the complete absence of symmetry. However, many chiral molecules have one or more proper rotation axes-just no improper axes are present. These compounds can be referred to as dissymmetric, essential a synonym for chiral. Thus, while all asymmetric molecules are chiral, not all chiral molecules are asymmetric. 6.3 Topicity relationship Topicity: derived from the same roots as topography and topology, relating to the spatial position of an object. 6.3.1 Homotopic, enantiotopic, and diastereotopic Homotopic: is defined as interconvertable by a Cn axis of the molecule. homotopic hydrogens homotopic hydrogens H H H H chiral influence cannot HO OH distinguish these methyl groups achiral molecules C2 Heterotopic: the same groups or atoms in inequivalent constitutional or stereochemical environment. - Enantiotopic: interconverted by an Sn axis of the molecule (n = 1 in this case). enantiotopic groups, when exposed to a chiral influence (chiral shift reagent를 사용할 시), become distinguishable, as if they were diastereotopic. - diastereotopic: the same connectivity, but there is no symmetry operation that interconverts them in any conformation. 이미 stereogenic center를갖고있음 the environments of diastereotopic groups are topologically nonequivalent. -> they can be distinguished by physical probes, especially NMR spectroscopy (AB quartet) diastereotopic H HS R - CO2 + NH3 phenylalanine meso: achiral chiral Me N Me Me N Me H H H H enantiotopic Ph Ph diastereotopic 2H H1 H2 AB quartet 6.3.2 Topicity descriptors – Pro-R/Pro-S and Re/Si 1 O Re face Si face R2 pro-S R1 pro-R 2 3 pro-S pro-R pro-S pro-R Enzymatic reactions pro-S pro-R H pro-S H H liver alcohol dehydrogenase H3C OH O -pro-R H3C ethanol acetaldehyde H Dor T T ro D H H3C OH H3C OH alcohol dehydrogenase H D or T O H C O H3C 3 pro-R H H H acyl-CoA dehydrogenase SCoA SCoA R R - pro-R α− and β−H H H O H O pro-R 6.4 Reaction stereochemistry: stereoselectivity and stereospecificity 6.4.1 Simple guidelines for reaction stereochemistry 1. Homotopic groups cannot be differentiated by chiral reagents. 2. Enantiotopic groups can be differentiated by chiral reagents. 3. Diastereotopic groups are differentiated by achiral and chiral reagents. 6.4.2 Stereospecific and stereoselective reactions Stereospecific reaction: one stereoisomer of the reactant gives one stereoisomer of the product, while a different stereoisomer of the reactant gives a different stereoisomer of product. Stereospecific reaction is a special, more restrictive case of a stereoselective reaction.
Recommended publications
  • Enantiotopicity, Diastereotopicity

    Enantiotopicity, Diastereotopicity

    Stereochemistry and stereocontrolled synthesis (OC 8) A lecture from Prof. Paul Knochel, Ludwig-Maximilians-Universität München WS 2015-16 1 Wichtig! • Prüfung Stereochemistry 02. Februar 2016 8:00 – 10:00 Willstätter-HS • Nachholklausur Stereochemistry 5. April 2016 9:00 – 11:00 Willstätter-HS 2 Problem set part I 3 Problem set part II 4 Problem set part III 5 Recommended Literature • E. Juaristi, Stereochemistry and Conformational Analysis, Wiley, 1991. • E. Eliel, Stereochemistry of Organic Compounds, Wiley, 1994. • A. Koskinen, Asymmetric Synthesis of Natural Products, Wiley, 1993. • R. Noyori, Asymmetric Catalysis, Wiley, 1994. • F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, 5th Edition, Springer, 2007. • A. N. Collins, G. N. Sheldrake, J. Crosby, Chirality in Industrie, Vol. I and II, Wiley, 1995 and 1997. • G.Q. Lin, Y.-M. Li, A.S.C. Chan, Asymmetric Synthesis, 2001, ISBN 0-471-40027-0. • P. Deslongchamps, Stereoelectronic Effects in Organic Chemistry, Pergamon, 1983. • M. Nogradi, Stereoselective Synthesis, VCH, 1995. • E. Winterfeldt, Stereoselective Synthese, Vieweg, 1988. • R. Mahrwald (Ed.), Modern Aldol Reactions, Vol. I and II, Wiley, 2004. • C. Wolf, Dynamic Stereochemistry of Chiral Compounds, RSC Publishing, 2008. • A. Berkessel, H. Gröger, Asymmetric Organocatalysis, Wiley-VCH, 2005. • J. Christoffers, A. Baro (Eds.), Quaternary Stereocenters, Wiley-VCH, 2005. • Catalytic Asymmetric Synthesis, I. Oshima (Ed.), Wiley, 2010. 6 Recent advances of asymmetric catalysis 7 Asymmetric Hydrogenation of Heterocyclic Compounds 8 R. Kuwano, N. Kameyama, R. Ikeda, J. Am. Chem. Soc. 2011, 133, 7312-7315. Camphor-Derived Organocatalytic Synthesis of Chromanones 9 Z.-Q. Rong, Y. Li, G.-Q. Yang, S.-L. You, Synlett 2011, 1033-1037.
  • Organic Chemistry

    Organic Chemistry

    Wisebridge Learning Systems Organic Chemistry Reaction Mechanisms Pocket-Book WLS www.wisebridgelearning.com © 2006 J S Wetzel LEARNING STRATEGIES CONTENTS ● The key to building intuition is to develop the habit ALKANES of asking how each particular mechanism reflects Thermal Cracking - Pyrolysis . 1 general principles. Look for the concepts behind Combustion . 1 the chemistry to make organic chemistry more co- Free Radical Halogenation. 2 herent and rewarding. ALKENES Electrophilic Addition of HX to Alkenes . 3 ● Acid Catalyzed Hydration of Alkenes . 4 Exothermic reactions tend to follow pathways Electrophilic Addition of Halogens to Alkenes . 5 where like charges can separate or where un- Halohydrin Formation . 6 like charges can come together. When reading Free Radical Addition of HX to Alkenes . 7 organic chemistry mechanisms, keep the elec- Catalytic Hydrogenation of Alkenes. 8 tronegativities of the elements and their valence Oxidation of Alkenes to Vicinal Diols. 9 electron configurations always in your mind. Try Oxidative Cleavage of Alkenes . 10 to nterpret electron movement in terms of energy Ozonolysis of Alkenes . 10 Allylic Halogenation . 11 to make the reactions easier to understand and Oxymercuration-Demercuration . 13 remember. Hydroboration of Alkenes . 14 ALKYNES ● For MCAT preparation, pay special attention to Electrophilic Addition of HX to Alkynes . 15 Hydration of Alkynes. 15 reactions where the product hinges on regio- Free Radical Addition of HX to Alkynes . 16 and stereo-selectivity and reactions involving Electrophilic Halogenation of Alkynes. 16 resonant intermediates, which are special favor- Hydroboration of Alkynes . 17 ites of the test-writers. Catalytic Hydrogenation of Alkynes. 17 Reduction of Alkynes with Alkali Metal/Ammonia . 18 Formation and Use of Acetylide Anion Nucleophiles .
  • Enantiotopic Discrimination in the NMR Spectrum of Prochiral Solutes in Chiral Liquid Crystals

    Enantiotopic Discrimination in the NMR Spectrum of Prochiral Solutes in Chiral Liquid Crystals

    Chemical Society Reviews Enantiotopic Discrimination in the NMR Spectrum of Prochiral Solutes in Chiral Liquid Crystals Journal: Chemical Society Reviews Manuscript ID: CS-REV-07-2014-000260 Article Type: Review Article Date Submitted by the Author: 29-Jul-2014 Complete List of Authors: Lesot, Phillippe; Universite Paris Sud (Paris XI), LRMN, ICMMO, UMR 8182 Aroulanda, Christie; Universite Paris Sud (Paris XI), LRMN, ICMMO, UMR 8182 Zimmermann, Herbert; Abteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Luz, Zeev; Weizmann Institute of Science, Department of Chemical Physics Page 1 of 117 Chemical Society Reviews Chem. Soc. Rev. (2014) - 1 - Enantiotopic Discrimination in the NMR Spectrum of Prochiral Solutes in Chiral Liquid Crystals Philippe Lesot* ,a , Christie Aroulanda a, Herbert Zimmermann b and Zeev Luz c a Laboratoire de RMN en Milieu Orienté CNRS UMR 8182, ICMMO, Bât. 410, Université de Paris-Sud, 91405 Orsay cedex, France. bAbteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany. c Weizmann Institute of Science, Department of Chemical Physics, Rehovot 76100, Israel. Corresponding author : Philippe Lesot: [email protected] Keywords : Prochirality, Enantiotopic sites, NMR, Chiral Liquid Crystals, Dynamics. Type of article : (comprehensive) review Chemical Society Reviews Page 2 of 117 Chem. Soc. Rev. (2014) - 2 - Abstract The splitting of signals in the NMR spectra originating from enantiotopic sites in prochiral molecules when dissolved in chiral solvents is referred to as spectral enantiotopic discrimination. The phenomenon is particularly noticeable in chiral liquid crystals (CLC) due to the combined effect of the anisotropic magnetic interactions and the ordering of the solute in the mesophase.
  • The Control of Stereochemistry by the Pentafluorosulfanyl Group

    The Control of Stereochemistry by the Pentafluorosulfanyl Group

    Organic & Biomolecular Chemistry View Article Online PAPER View Journal | View Issue The control of stereochemistry by the pentafluorosulfanyl group† Cite this: Org. Biomol. Chem., 2018, 16, 3151 Paul R. Savoie, Cortney N. von Hahmann, Alexander Penger, Zheng Wei and John T. Welch * The influence of pentafluorosulfanylation on biological activity has been revealed in numerous compara- tive studies of biologically active compounds, but considerably less is known about the influence of pen- tafluorosulfanylation on reactivity. Among the distinctive properties of the pentafluorosulfanyl group is the profound dipole moment that results from introduction of this substituent. It has been shown that dipolar Received 20th December 2017, effects coupled with the steric demand of the SF5 group may be employed to influence the stereo- Accepted 3rd April 2018 chemistry of reactions, especially those processes with significant charge separation in the transition DOI: 10.1039/c7ob03146g state. The Staudinger ketene-imine cycloaddition reaction is an ideal platform for investigation of dipolar rsc.li/obc control of diastereoselectivity by the pentafluorosulfanyl group. Introduction ation into a hydrocarbon chain, the restricted rotation about the carbon–sulfur bond that results from interactions with Numerous pentafluorosulfanyl(SF5)-containing organic nearby methylene groups, can lead to localized conformational – compounds1 10 have been prepared that have potential utility rigidity of the alkyl chain.21,22 in drug discovery, agrochemical synthesis and materials
  • The Use of Spirocyclic Scaffolds in Drug Discovery ⇑ Yajun Zheng , Colin M

    The Use of Spirocyclic Scaffolds in Drug Discovery ⇑ Yajun Zheng , Colin M

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Bioorganic & Medicinal Chemistry Letters 24 (2014) 3673–3682 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl BMCL Digest The use of spirocyclic scaffolds in drug discovery ⇑ Yajun Zheng , Colin M. Tice, Suresh B. Singh Vitae Pharmaceuticals Inc., 502 West Office Center Drive, Fort Washington, PA 19034, United States article info abstract Article history: Owing to their inherent three-dimensionality and structural novelty, spiro scaffolds have been increas- Received 15 April 2014 ingly utilized in drug discovery. In this brief review, we highlight selected examples from the primary Revised 17 June 2014 medicinal chemistry literature during the last three years to demonstrate the versatility of spiro scaffolds. Accepted 27 June 2014 With recent progress in synthetic methods providing access to spiro building blocks, spiro scaffolds are Available online 5 July 2014 likely to be used more frequently in drug discovery. Ó 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND Keywords: license (http://creativecommons.org/licenses/by-nc-nd/3.0/). Spirocyclic Scaffold Drug discovery One widely used strategy in drug design is to rigidify the ligand present in a number of bioactive natural products such as mito- conformation by introducing a ring.1 The resulting cyclic analog mycins, it is generally difficult to construct such aziridines from will suffer a reduced conformational entropy penalty upon binding unfunctionalized olefins. A recent report of a facile synthetic route to a protein target.
  • Chapter 77 These Powerpoint Lecture Slides Were Created and Prepared by Professor William Tam and His Wife, Dr

    Chapter 77 These Powerpoint Lecture Slides Were Created and Prepared by Professor William Tam and His Wife, Dr

    About The Authors Chapter 77 These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang. Professor William Tam received his B.Sc. at the University of Hong Kong in Alkenes and Alkynes I: 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard Properties and Synthesis. University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards Elimination Reactions in research and teaching, and according to Essential Science Indicators , he is currently ranked as the Top 1% most cited Chemists worldwide. He has of Alkyl Halides published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem. Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her Created by M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew. Professor William Tam & Dr. Phillis Chang Ch. 7 - 1 Ch. 7 - 2 1. Introduction Alkynes ● Hydrocarbons containing C ≡C Alkenes ● Common name: acetylenes ● Hydrocarbons containing C=C H ● Old name: olefins N O I Cl C O C O CH2OH Cl F3C C Cl Vitamin A C H3C Cl H3C HH Efavirenz Haloprogin Cholesterol (antiviral, AIDS therapeutic) (antifungal, antiseptic) HO Ch.
  • Aldehydes and Ketones

    Aldehydes and Ketones

    Organic Lecture Series Aldehydes And Ketones Chap 16 111 Organic Lecture Series IUPAC names • the parent alkane is the longest chain that contains the carbonyl group • for ketones, change the suffix -e to -one • number the chain to give C=O the smaller number • the IUPAC retains the common names acetone, acetophenone, and benzophenone O O O O Propanone Acetophenone Benzophenone 1-Phenyl-1-pentanone (Acetone) Commit to memory 222 Organic Lecture Series Common Names – for an aldehyde , the common name is derived from the common name of the corresponding carboxylic acid O O O O HCH HCOH CH3 CH CH3 COH Formaldehyde Formic acid Acetaldehyde Acetic acid – for a ketone , name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone O O O Ethyl isopropyl ketone Diethyl ketone Dicyclohexyl ketone 333 Organic Lecture Series Drawing Mechanisms • Use double-barbed arrows to indicate the flow of pairs of e - • Draw the arrow from higher e - density to lower e - density i.e. from the nucleophile to the electrophile • Removing e - density from an atom will create a formal + charge • Adding e - density to an atom will create a formal - charge • Proton transfer is fast (kinetics) and usually reversible 444 Organic Lecture Series Reaction Themes One of the most common reaction themes of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound (intermediate). - R O Nu - + C O Nu C R R R Tetrahedral carbonyl addition compound 555 Reaction Themes Organic Lecture Series A second common theme is
  • Chapter 8. Chiral Catalysts José M

    Chapter 8. Chiral Catalysts José M

    Chapter 8. Chiral Catalysts José M. Fraile, José I. García, José A. Mayoral 1. The Origin of Enantioselectivity in Catalytic Processes: the Nanoscale of Enantioselective Catalysis. Enantiomerically pure compounds are extremely important in fields such as medicine and pharmacy, nutrition, or materials with optical properties. Among the different methods to obtain enantiomerically pure compounds, asymmetric catalysis1 is probably the most interesting and challenging, in fact one single molecule of chiral catalyst can transfer its chiral information to thousands or even millions of new chiral molecules. Enantioselective reactions are the result of the competition between different possible diastereomeric reaction pathways, through diastereomeric transition states, when the prochiral substrate complexed to the chiral catalyst reacts with the corresponding reagent. The efficiency of the chirality transfer, measured as enantiomeric excess [% ee = (R−S)/(R+S) × 100], depends on electronic and steric factors in a very subtle form. A simple calculation shows that differences in energy of only 2 kcal/mol between these transition states are enough to obtain more than 90% ee, and small changes in any of the participants in the catalytic process can modify significantly this difference in energy. Those modifications may occur in the near environment of the catalytic centre, at less than 1 nm scale, but also at longer distances in the catalyst, substrate, reagent, solvent, or support in the case of immobilized catalysts. This is the reason because asymmetric
  • 13C-13C Vicinal Coupling Constan

    13C-13C Vicinal Coupling Constan

    Proc. Nat. Acad. Sci. USA Vol. 72, No. 12, pp. 4948-4952, December 1975 Biophysics 13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue (hypothalamic hormone/13C labeling/pH effects/angular dependence/pyrrolidine ring puckering) WOLFGANG HAAR*, SERGE FERMANDJIAN*§, JAROSLAV VICARt, KAREL BLAHAf, AND PIERRE FROMAGEOT* * Service de Biochimie, Centre d'Etudes Nucleaires de Saclay, B.P. no. 2, 91190-GIF-sur-Yvette, France; t Institute of Organic Chemistry and Biochemistry, Flemingoro Namesti 2, Prague, Czechoslovakia; and * Institute for Medical Chemistry, Palacky University, Olomouc, Czechoslovakia Communicated by Irvtine H. Page, September 22, 1975 ABSTRACT To understand fully interactions between with a natural peptide containing a single '3C-enriched peptides and cellular receptors, peptide side chain conforma- amino acid. In previous papers, we have demonstrated that tion must be defined. In many cases the complexity of proton 85% '3C-enrichment of amino acids offers several advan- nuclear magnetic resonance (NMR) prevents this but the tages (25-27) when compared to unenriched samples. Not present work demonstrates this problem can be solved by also those of using 13C enrichment. Selective '3C enrichment of a natural only are problems of concentration solved, but peptide hormone has been achieved by preparing [85% '3C signal assignment if only one amino acid is selectively la- enriched prolinelthyrotropin releasing factor which was ex- beled in the peptide. Furthermore '3C-'3C coupling con- amined by '3C NMR spectroscopy at various pH values. Be- stants, undetectable with unenriched samples, are easily cause of the '3C enrichment, one-bonded and three-bonded measured (28-89).
  • Transition Metal-Free Homologative Cross-Coupling of Aldehydes and Ketones with Geminal Bis(Boron) Compounds Thomas C

    Transition Metal-Free Homologative Cross-Coupling of Aldehydes and Ketones with Geminal Bis(Boron) Compounds Thomas C

    Transition metal-free homologative cross-coupling of aldehydes and ketones with geminal bis(boron) compounds Thomas C. Stephens and Graham Pattison* Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. Supporting Information Placeholder ABSTRACT: We report a transition metal-free coupling of aldehydes and ketones with geminal bis(boron) building blocks which provides the coupled, homologated carbonyl compound upon oxidation. This reaction not only extends an alkyl chain containing a carbonyl group, it also simultaneously introduces a new carbonyl substituent. We demonstrate that enantiopure aldehydes with an enolizable stereogenic centre undergo this reaction with complete retention of stereochemistry. A range of coupling processes, both metal-catalyzed and proceed with a very high degree of stereocontrol over double metal-free, are transforming the way chemists build mole- bond geometry. 1 cules. Transition metal-free coupling processes are of particu- The key to our general synthetic strategy was the realization lar attraction due to very stringent requirements for low ppm that oxidation of this vinyl boronate will afford a homologated values of toxic transition metal residues in pharmaceutical aldehyde or ketone. Carbonyl compounds have proven to be products. As a result, a series of such transition metal-free some of the key mainstays of organic synthesis over the years, coupling processes are beginning to emerge, using in particu- being found in a broad range of biologically active compounds lar readily available building blocks such as organoboron as well as being key substrates for the synthesis of many alco- 2,3 compounds. hols, heterocycles and enolate condensation products. One class of organoboron building block which is seeing Homologation reactions of carbonyl compounds are significant recent attention are geminal-bis(boronates).
  • Gas-Phase Water-Mediated Equilibrium Between Methylglyoxal

    Gas-Phase Water-Mediated Equilibrium Between Methylglyoxal

    Gas-phase water-mediated equilibrium between SPECIAL FEATURE methylglyoxal and its geminal diol Jessica L. Axsona,b, Kaito Takahashic, David O. De Haand, and Veronica Vaidaa,b,1 aDepartment of Chemistry and Biochemistry, and bCooperative Institute for Research in Environmental Sciences, Campus Box 215, University of Colorado, Boulder, CO 80309; cThe Institute of Atomic and Molecular Sciences, P.O. Box 23-166, Taipei, Taiwan 10617, Republic of China; and dDepartment of Chemistry and Biochemistry, University of San Diego, 5998 Alcala Park, San Diego, CA 92110 Edited by Barbara J. Finlayson-Pitts, University of California, Irvine, CA, and approved December 15, 2009 (received for review October 20, 2009) In aqueous solution, aldehydes, and to a lesser extent ketones, mined computationally that the aldehydic C ¼ O is more favor- −1 hydrate to form geminal diols. We investigate the hydration of ably hydrated in solution (ΔG ¼ −1.4 kcal mol ) than the −1 methylglyoxal (MG) in the gas phase, a process not previously ketonic C ¼ O(ΔG ¼þ2.5 kcal mol ) (21). In solution, MG considered to occur in water-restricted environments. In this study, is present primarily as MGD (60% diol to 40% tetrol) with we spectroscopically identified methylglyoxal diol (MGD) and the aldehydic group forming a geminal diol (21, 23). MGD obtained the gas-phase partial pressures of MG and MGD. These has a lower vapor pressure than MG, which allows the molecule results, in conjunction with the relative humidity, were used to ob- to partition more easily into the particle phase, lending to the tain the equilibrium constant, KP, for the water-mediated hydration formation of SOA.
  • 3.1. Nomenclature of Proteins and Nucleic Acids

    3.1. Nomenclature of Proteins and Nucleic Acids

    Structure Determination by NMR Spectroscopy #3-1 3. Computational methods in NMR-spectroscopy 3.1 Nomenclature of proteins and nucleic acids 3.1.1. Classification of structural relationships between molecules For the description of small organic molecules several notations were introduced to classify the chemical and structural relations. These are: isomer, constitutional isomer, stereoisomer, enantiomer and diastereomer. The following flow-chart has been designed to find the stereo- chemical relationship between two molecules. molecules of equal atom composition (same molecular formula) yes no coinciding atom positions ? homomers isomers (identical) yes equal constitution ? stereoisomer yes no no mirror images not coinciding ? enantiomers diastereomers constitutional isomer There are a lot of computer programs performing various kinds of structure calculations for biopolymers, which differ partially or substantially in the force fields or algorithms used. All programs, however, rely on structure relevant geometric data (covalent bound atoms, bond angles, dihedral angles, improper dihedral angles etc.) which build the topology of the bio- macromolecule building blocks often collected in a library file. Some stereochemical relati- onships are also reflected in the topology. The following terms should be distinguished when discussing structures: • constitutional isomers = molecules having an identical chemical formula but different bin- ding pattern. For instance, both valine and isovaline have the same chemical net formula but differ substantially in the covalent bonding pattern; Structure Determination by NMR Spectroscopy #3-2 Therefore, constitutional isomers will be found in the library as fragments with separate resi- due names. • configuration = spatial arrangements of atoms around a center of chirality [see tetrahe- dron], not to made identical without breaking a bond.