DOCSLIB.ORG

CHIRAL INTERMEDIATES (March 2001)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
CHIRAL INTERMEDIATES (March 2001) Abstract Process Economics Program Report 232 CHIRAL INTERMEDIATES (March 2001) Chiral chemicals are a unique class of compounds that, although chemically identical, exist as mirror images of each other called enantiomers. Chiral compounds touch many aspects of everyday life. The chirality of a compound affects how food tastes, how drugs interact in the body, and how quickly products decompose in the environment. Major identified markets for chi- ral compounds include: • Pharmaceuticals. • Agricultural chemicals. • Food and feed additives. • Polymers. Production methods for chiral compounds encompass many diverse technologies. This re- port reviews three major technologies for the production of chiral compounds: • Resolution by crystallization of diastereomers. • Resolution by enzymes. • Asymmetric synthesis by biocatalysis. PEP’98 RGB/TFM CONTENTS GLOSSARY ...................................................................................................................... xiii 1 INTRODUCTION ...................................................................................................... 1-1 2 SUMMARY................................................................................................................. 2-1 NAPROXEN RESOLUTION BY CRYSTALLIZATION............................................... 2-1 1-PHENYLETHYLAMINE BY ENZYMATIC RESOLUTION.......................................2-2 D-PHENYLALANINE BY BIOCATALYTIC CONVERSION........................................2-2 ECONOMICS ............................................................................................................. 2-2 PROCESS MATURITY ..............................................................................................2-4 TOTAL FIXED CAPITAL............................................................................................ 2-4 CONCLUSIONS......................................................................................................... 2-5 3 INDUSTRY STATUS..................................................................................................3-1 PHARMACEUTICALS................................................................................................ 3-1 AGROCHEMICALS.................................................................................................... 3-2 FOOD, FLAVORS, AND FEED ADDITIVES..............................................................3-2 SPECIALTY POLYMERS........................................................................................... 3-2 PRODUCERS OF CHIRAL CHEMICALS AND THEIR TECHNOLOGIES................ 3-2 4 CHEMISTRY.............................................................................................................. 4-1 INTRODUCTION .......................................................................................................4-1 HISTORY AND NOMENCLATURE ........................................................................... 4-1 Enantiomeric Excess..................................................................................................4-2 Racemization ............................................................................................................. 4-3 Chiral Sources ...........................................................................................................4-3 Chiral Pool.................................................................................................................. 4-3 Resolution by Crystallization ...................................................................................... 4-3 Production of Resolving Agent................................................................................... 4-4 Reaction of Resolving Agent and Naproxen ..............................................................4-5 iii CONTENTS (Continued) 4 CHEMISTRY (Concluded) Recovery of Resolving Agent.....................................................................................4-6 Recovery of Product ..................................................................................................4-7 Racemization of R-Naproxen .....................................................................................4-7 ENZYMATIC RESOLUTION OF RACEMIC MIXTURES........................................... 4-7 Enzyme Catalysis.......................................................................................................4-8 D-PHENYLALANINE SYNTHESIS BY BIOCATALYSIS ........................................... 4-9 5 NAPROXEN RESOLUTION BY CRYSTALLIZATION............................................... 5-1 INTRODUCTION .......................................................................................................5-1 PROCESS REVIEW ..................................................................................................5-1 Classical Resolution...................................................................................................5-1 Crystallization of Conglomerates ............................................................................... 5-1 Crystallization of Racemic Compounds ..................................................................... 5-3 PROCESS DESCRIPTION........................................................................................ 5-5 Overview of the Process ............................................................................................ 5-5 Section 100—Resolution and Racemization..............................................................5-6 Recrystallization.................................................................................................... 5-6 Racemization and Recycle.................................................................................... 5-7 Section 200—Regeneration of Resolving Agent........................................................ 5-7 Section 300—Product Recovery ................................................................................5-7 PROCESS DISCUSSION ..........................................................................................5-18 Product Recovery.......................................................................................................5-19 Racemization ............................................................................................................. 5-19 Waste Generation ...................................................................................................... 5-19 Materials of Construction ........................................................................................... 5-19 CAPITAL AND PRODUCTION COSTS..................................................................... 5-19 Capital Costs.............................................................................................................. 5-20 Production Costs........................................................................................................ 5-20 iv CONTENTS (Continued) 6 SEPARATION OF CHIRAL AMINES BY ENZYMATIC TRANSFORMATION........... 6-1 INTRODUCTION .......................................................................................................6-1 CHEMISTRY.............................................................................................................. 6-1 Enzyme Catalysis.......................................................................................................6-1 PROCESS REVIEW ..................................................................................................6-3 Hydrolysis of Amide.................................................................................................... 6-3 Racemization ............................................................................................................. 6-4 PROCESS DESCRIPTION........................................................................................ 6-5 Enzymatic Resolution................................................................................................. 6-5 Acylation ............................................................................................................... 6-5 Separations ...........................................................................................................6-5 Amide Hydrolysis ..................................................................................................6-6 Re-Esterification......................................................................................................... 6-6 Racemization ............................................................................................................. 6-6 PROCESS DISCUSSION ..........................................................................................6-21 Acylation ....................................................................................................................6-21 Distillation/Separation ................................................................................................ 6-21 Amide Hydrolysis .......................................................................................................6-21 Ester Regeneration .................................................................................................... 6-21 Waste Streams...........................................................................................................6-21 Liquid ....................................................................................................................6-21 Solid .....................................................................................................................
Load more

Recommended publications
  • Chiral Auxiliaries and Optical Resolving Agents
    Chiral Auxiliaries and Optical Resolving Agents Most bioactive substances are optically active. For instance, if This brochure introduces a variety of chiral auxiliaries and a substance is synthesized as a racemic compound, its optical resolving agents. We hope that it will be useful for your enantiomer may show no activity or even undesired bioactivity. research of the synthesis of optically active compounds. Thus, methods to gain enantiopure compounds have been Additionally, TCI has some brochures introducing chiral developed. When synthesizing enantiopure compounds, the compounds for the chiral pool method in “Chiral Building Blocks”, methods are roughly divided into three methods. “Terpenes”, “Amino Acids” and other brochures. Sugar derivatives are also introduced in a catalog, “Reagents for Glyco Chemistry Chiral pool method: & Biology”, and category pages of sugar chains. Furthermore, The method using an easily available chiral compound as a TCI has many kinds of catalysts for asymmetric synthesis and starting material like an amino acid or sugar. introduce them in brochures such as “Asymmetric Synthesis” and Asymmetric synthesis: “Asymmetric Organocatalysts”, and other contents. The method to introduce an asymmetric point to compounds You can search our information through “asymmetric synthesis” without an asymmetric point. Syntheses using achiral as a keyword. auxiliaries are included here. Optical resolution: The method to separate a racemic compound into two ● Reactions with Chiral Auxiliaries enantiomers. The direct method using a chiral column and One of the most famous named reactions using chiral auxiliaries1) the indirect method to separate two enantiomers using is the Evans aldol reaction.2) This reaction is quite useful because optical resolving agents to convert into diastereomers are this reaction can efficiently introduce two asymmetric carbons into examples.
    [Show full text]
  • Separation of the Mixtures of Chiral Compounds by Crystallization
    1 Separation of the Mixtures of Chiral Compounds by Crystallization Emese Pálovics2, Ferenc Faigl1,2 and Elemér Fogassy1* 1Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 2Research Group for Organic Chemical Technology, Hungarian Academy of Sciences, Budapest, Hungary 1. Introduction Reaction of a racemic acid or base with an optically active base or acid gives a pair of diastereomeric salts. Members of this pair exhibit different physicochemical properties (e.g., solubility, melting point, boiling point, adsorbtion, phase distribution) and can be separated owing to these differences. The most important method for the separation of enantiomers is the crystallization. This is the subject of this chapter. Preparation of enantiopure (ee~100%) compounds is one of the most important aims both for industrial practice and research. Actually, the resolution of racemic compounds (1:1 mixture of molecules having mirror-imagine relationship) still remains the most common method for producing pure enantiomers on a large scale. In these cases the enantiomeric mixtures or a sort of their derivatives are separated directly. This separation is based on the fact that the enantiomeric ratio in the crystallized phase differs from the initial composition. In this way, obtaining pure enantiomers requires one or more recrystallizations. (Figure 1). The results of these crystallizations (recrystallizations) of mixtures of chiral compounds differ from those observed at the achiral compounds. Expectedly, not only the stereoisomer in excess can be crystallized, because the mixture of enantiomers (with mirror image relationship) follows the regularities established from binary melting point phase diagrams, and ternary composition solubility diagrams, respectively, as a function of the starting enantiomer proportion.
    [Show full text]
  • II. Stereochemistry 5
    B.Sc.(H) Chemistry Semester - II Core Course - III (CC-III) Organic Chemistry - I II. Stereochemistry 5. Physical and Chemical Properties of Stereoisomers Dr. Rajeev Ranjan University Department of Chemistry Dr. Shyama Prasad Mukherjee University, Ranchi 1 Syllabus & Coverage Syllabus II Stereochemistry: Fischer Projection, Newmann and Sawhorse Projection formulae and their interconversions. Geometrical isomerism: cis–trans and syn-anti isomerism, E/Z notations with Cahn Ingold and Prelog (CIP) rules for determining absolute configuration. Optical Isomerism: Optical Activity, Specific Rotation, Chirality/Asymmetry, Enantiomers, Molecules with two or more chiral-centres, Distereoisomers, Meso structures, Racemic mixture. Resolution of Racemic mixtures. Relative and absolute configuration: D/L and R/S designations. Coverage: 1. Types of Isomers : Comparing Structures 2. Optical Activity 3. Racemic Mixtures : Separation of Racemic Mixtures 4. Enantiomeric Excess and Optical Purity 5. Relative and Absolute Configuration 6. Physical and Chemical Properties of Stereoisomers 2 Stereochemistry Types of Isomers Dr. Rajeev Ranjan 3 Stereochemistry Determining the Relationship Between Two Non-Identical Molecules Dr. Rajeev Ranjan 4 Stereochemistry Comparing Structures: Are the structures connected the same? yes no Are they mirror images? Constitutional Isomers yes no Enantiomers Enantiomers Is there a plane of symmetry? All chiral centers will be opposite between them. yes no Meso Diastereomers superimposable Dr. Rajeev Ranjan 5 Stereochemistry Optical Activity: • The chemical and physical properties of two enantiomers are identical except in their interaction with chiral substances. • The physical property that differs is the behavior when subjected to plane-polarized light ( this physical property is often called an optical property). • Plane-polarized (polarized) light is light that has an electric vector that oscillates in a single plane.
    [Show full text]
  • Cross-Linked Protein Crystal Technology in Bioseparation and Biocatalytic Applications
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Aaltodoc Helsinki University of Technology, Department of Chemical Technology Technical Biochemistry Report 1/2004 Espoo 2004 TKK-BE-8 CROSS-LINKED PROTEIN CRYSTAL TECHNOLOGY IN BIOSEPARATION AND BIOCATALYTIC APPLICATIONS Antti Vuolanto Dissertation for the degree of Doctor in Science in Technology to be presented with due permission of the Department of Chemical Technology for public examination and debate in Auditorium KE 2 (Komppa Auditorium) at Helsinki University of Technology (Espoo, Finland) on the 20th of August, 2004, at 12 noon. Helsinki University of Technology Department of Chemical Technology Laboratory of Bioprocess Engineering Teknillinen korkeakoulu Kemian osasto Bioprosessitekniikan laboratorio Distribution: Helsinki University of Technology Laboratory of Bioprocess Engineering P.O. Box 6100 FIN-02015 HUT Tel. +358-9-4512541 Fax. +358-9-462373 E-mail: [email protected] ©Antti Vuolanto ISBN 951-22-7176-1 (printed) ISBN 951-22-7177-X (pdf) ISSN 0359-6621 Espoo 2004 Vuolanto, Antti. Cross-linked protein crystal technology in bioseparation and biocatalytic applications. Espoo 2004, Helsinki University of Technology. Abstract Chemical cross-linking of protein crystals form an insoluble and active protein matrix. Cross-linked protein crystals (CLPCs) have many excellent properties including high volumetric activity and stability. In this thesis CLPC technology was studied in bioseparation and biocatalytic applications. A novel immunoaffinity separation material, cross-linked antibody crystals (CLAC), was developed in this thesis for enantiospecific separation of a chiral drug, finrozole. Previously, the preparation of an antibody Fab fragment ENA5His capable of enantiospecific affinity separation of the chiral drug has been described.
    [Show full text]
  • The Racemate-To-Homochiral Approach to Crystal Engineering Via Chiral Symmetry-Breaking
    CrystEngComm The Racemate -to -Homochiral Approach to Crystal Engineering via Chiral Symmetry-Breaking Journal: CrystEngComm Manuscript ID: CE-HIG-02-2015-000402.R1 Article Type: Highlight Date Submitted by the Author: 04-Apr-2015 Complete List of Authors: An, Guanghui; Heilongjiang University, School of Chemistry and Materials Science Yan, Pengfei; Heilongjiang University, School of Chemistry and Materials Science Sun, Jingwen; Heilongjiang University, School of Chemistry and Materials Science Li, Yuxin; School of Chemsitry and Materials Science of Heilongjiang University, Yao, Xu; Heilongjiang University, School of Chemistry and Materials Science Li, Guangming; School of Chemsitry and Materials Science of Heilongjiang University, Page 1 of 12Journal Name CrystEngComm Dynamic Article Links ► Cite this: DOI: 10.1039/c0xx00000x www.rsc.org/xxxxxx ARTICLE TYPE The Racemate-to-Homochiral Approach to Crystal Engineering via Chiral Symmetry-Breaking Guanghui An, a Pengfei Yan, a Jingwen Sun, a Yuxin Li, a Xu Yao, a Guangming Li,* a Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5 DOI: 10.1039/b000000x The racemate-to-homochiral approach is to transform or separate the racemic mixture into homo chiral compounds. This protocol, if without an external chiral source, is categorized into chiral symmetry- breaking. The resolution processes without chiral induction are highly important for the investigation on the origin of homochirality in life, pharmaceutical synthesis, chemical industrial and material science. 10 Besides the study on the models and mechanisms to explain the racemate-to-homochiral approach which may give the probable origin of homochirality in life, the recent developments in this field have been plotted towards the separation of enantiomers for the synthesis of pharmaceuticals, chiral chemicals.
    [Show full text]
  • Lectures 2014
    Selective Organic Synthesis KD 2390 (9 hp) Christina Moberg The advent of organic chemistry shaped the world • Biology is dependent on organic synthesis • Organic synthesis is the foundation for biotechnology, nanotechnology, pharmaceutical industry, and material industry About the course: • Disposition: lectures, exercises, lab, workshop • Course book: Clayden, Greeves and Warren Organic Chemistry, Oxford University Press, 2012 (ISBN 978-0-19-927029-3) [or Clayden, Greeves, Warren and Wothers: Organic Chemistry, Oxford University Press, 2001 (ISBN 0 19 850346 6)] and distributed material • Examination: oral exam, lab work (lab and workshop compulsory) After the course the student should be able to:" " • Describe basic stereochemical concepts • Describe principles for stereoselective synthesis, in particular for enantioselective synthesis • Explain the stereochemistry observed in chemical reactions • Suggest methods for stereoselective synthesis of simple organic compounds containing stereogenic elements • Identify suitable reagents for stereoselective transformations • Use retrosynthetic analysis for the construction of synthetic routes for simple organic compounds • Prepare organic compounds using advanced synthetic methodology Contents • Fundamental stereochemical concepts • Synthetic strategy and principles for stereoselective, in particular enantioselective, chemical transformations • Transition metal catalysis • Applications of frontier orbital theory • Retrosynthetic analysis • Advanced organic synthesis Marcellin Pierre Eugène Berthelot (1827 - 1907) " "La Chimie crée ses objets" “This is an important point: neither biology nor chemistry would be served best by a development in which all organic chemists would simply become biological such that, as a consequence, research at the core of organic chemistry and, therefore, progress in understanding the reactivity of organic molecules, would dry out. Progress at its core in understanding and reasoning in not only essential for organic chemistry itself, but for life sciences as a whole.
    [Show full text]
  • Practical Aspects on How to Deracemize Atropizomers by Means of Crystallization Ryusei Oketani
    Practical aspects on how to deracemize atropizomers by means of crystallization Ryusei Oketani To cite this version: Ryusei Oketani. Practical aspects on how to deracemize atropizomers by means of crystallization. Organic chemistry. Normandie Université, 2019. English. NNT : 2019NORMR109. tel-02502796 HAL Id: tel-02502796 https://tel.archives-ouvertes.fr/tel-02502796 Submitted on 9 Mar 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE Pour obtenir le diplôme de doctorat Spécialité Chimie Préparée au sein de l’Université de Rouen Normandie Practical aspects on how to deracemize atropisomers by means of crystallization (Aspects pratiques de la déracémisation d'atropisomères par cristallisation) Présentée et soutenue par Ryusei OKETANI Thèse soutenue publiquement le 06 Décembre 2019 devant le jury composé de M. Alexander BREDIKHIN Pr FRC Kazan Scientific Center of RAS Rapporteur M. Joop Ter HORST Pr University of Strathclyde Rapporteur M. Gérard COQUEREL Pr Université de Rouen Normandie Président Mme. Sylvie FERLAY-CHARITAT Pr Université de Strasbourg Examinateur M. Pascal CARDINAEL Pr Université de Rouen Normandie Directeur de thèse Thèse dirigée par Pascal CARDINAEL professeur des universités et Co-encadrée par le Dr. Clément BRANDEL au laboratoire Sciences et Méthodes Séparatives (EA3233 SMS) Contents Contents Contents .........................................................................................................................
    [Show full text]
  • Chapter 4: Stereochemistry Introduction to Stereochemistry
    Chapter 4: Stereochemistry Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane Me Me Me C Me H Bu Bu Me Me 2-methylhexane H H mirror Me rotate Bu Me H 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane H C Et Et Me Pr Pr 3-methylhexane Me Me H H mirror Et rotate H Me Pr 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane .Compounds that are not superimposable with their mirror image are called chiral (in Greek, chiral means "handed") 3-methylhexane is a chiral molecule. .Compounds that are superimposable with their mirror image are called achiral. 2-methylhexane is an achiral molecule. .An atom (usually carbon) with 4 different substituents is called a stereogenic center or stereocenter. Enantiomers Et Et Pr Pr Me CH3 Me H H 3-methylhexane mirror enantiomers Et Et Pr Pr Me Me Me H H Me H H Two compounds that are non-superimposable mirror images (the two "hands") are called enantiomers. Introduction To Stereochemistry Structural (constitutional) Isomers - Compounds of the same molecular formula with different connectivity (structure, constitution) 2-methylpentane 3-methylpentane Conformational Isomers - Compounds of the same structure that differ in rotation around one or more single bonds Me Me H H H Me H H H H Me H Configurational Isomers or Stereoisomers - Compounds of the same structure that differ in one or more aspects of stereochemistry (how groups are oriented in space - enantiomers or diastereomers) We need a a way to describe the stereochemistry! Me H H Me 3-methylhexane 3-methylhexane The CIP System Revisited 1.
    [Show full text]
  • Enzyme Supported Crystallization of Chiral Amino Acids
    ISBN 978-3-89336-715-3 40 Band /Volume Gesundheit /Health 40 Gesundheit Enzyme supported crystallization Health Kerstin Würges of chiral amino acids Mitglied der Helmholtz-Gemeinschaft Kerstin Würges Kerstin aminoacids Enzyme supported ofchiral crystallization Schriften des Forschungszentrums Jülich Reihe Gesundheit / Health Band / Volume 40 Forschungszentrum Jülich GmbH Institute of Bio- and Geosciences (IBG) Biotechnology (IBG-1) Enzyme supported crystallization of chiral amino acids Kerstin Würges Schriften des Forschungszentrums Jülich Reihe Gesundheit / Health Band / Volume 40 ISSN 1866-1785 ISBN 978-3-89336-715-3 Bibliographic information published by the Deutsche Nationalbibliothek. The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available in the Internet at http://dnb.d-nb.de. Publisher and Forschungszentrum Jülich GmbH Distributor: Zentralbibliothek 52425 Jülich Phone +49 (0) 24 61 61-53 68 · Fax +49 (0) 24 61 61-61 03 e-mail: [email protected] Internet: http://www.fz-juelich.de/zb Cover Design: Grafische Medien, Forschungszentrum Jülich GmbH Printer: Grafische Medien, Forschungszentrum Jülich GmbH Copyright: Forschungszentrum Jülich 2011 Schriften des Forschungszentrums Jülich Reihe Gesundheit / Health Band / Volume 40 D 61 (Diss. Düsseldorf, Univ., 2011) ISSN 1866-1785 ISBN 978-3-89336-715-3 The complete volume ist freely available on the Internet on the Jülicher Open Access Server (JUWEL) at http://www.fz-juelich.de/zb/juwel Neither this book nor any part of it may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
    [Show full text]
  • Preferential Crystallization of a Racemic Compound Via Its Conglomerate Co-Crystals
    Preferential crystallization of a racemic compound via its conglomerate co-crystals Master Thesis Oscar F. Villamil R August 24th 2016 Faculty of 3ME Department: Process & Energy Section: Intensified Reaction & Separation Systems Graduation Committee Ir. W. Li PDeng Dr. ir. H.J.M Kramer Dr. ir. H.W.Nugteren Dr. ir. A. van der Heijden 1 Abstract Preferential crystallization, as a powerful chiral resolution technique, is intrinsically limited to chiral molecules that crystallize as conglomerates. Many studies have been conducted on using chemical reactions to convert the target molecules, which originally form racemic compounds, into conglomerate-forming derivatives salts or by creating solvate, for the application of preferential crystallization. Up to this date conglomerate co-crystals of racemic compounds have never been applied as the intermediate for chiral resolution. In this study, preferential crystallization of the model compound Ibuprofen (IBU), originally a racemic compound, was carried out via its conglomerate co-crystal with 2,4-bipyridine ethylene (BPE) in heptane. Suitable operation conditions were selected based on pseudo- binary phase diagram of the model compound system constructed under different IBU-BPE ratio. A unique measurement method combining polarimeter and Nuclear Magnetic Resonance (NMR) measurements was developed to identify the enantiopurity and the yield of the final product, which was a mixture of racemic IBU and IBU-BPE co-crystals, a likely result from this complex system. With respect to the results, preferential crystallization of IBU was successfully performed by slowly cooling down a saturated solution of racemic IBU-BPE, initially at T=57.5°C, after seeding it with S-IBU/BPE crystals to T=53°C with a cooling rate of 0.3°C/min.
    [Show full text]
  • Catalytic Asymmetric Synthesis
    Catalytic Asymmetric Synthesis Dr Alan Armstrong Rm 313 (RCS1), ext. 45876; [email protected] 7 lectures Recommended texts: “Catalytic Asymmetric Synthesis, 2nd edition”, ed. I Ojima, Wiley-VCH, 2000 (or 1st ed., 1993, which contains most of the lecture material) “Asymmetric Synthesis”, G Procter, Oxford, 1996 Aims of course: To give students an understanding of the basic principles of asymmetric catalysis, and to demonstrate these in the context of state-of-the-art catalytic asymmetric processes for C-C bond formation and redox processes. Course objectives: At the end of this course you should be able to: • Recognise the types of functional groups which can be prepared by catalytic asymmetric methods discussed in the course; • Use this knowledge in planning the synthesis of enantiomerically enriched compounds from given prochiral starting materials; • Outline the scope and limitations of any methods you propose, with respect to parameters such as turnover, substrate and functional group tolerance, availability of catalysts and/or ligands etc Course content (by lecture, approximately): 1. Introduction and general principles of asymmetric catalysis. Oxidation of functionalised olefins: asymmetric epoxidation of allylic alcohols and enones 2. Oxidation of unfunctionalised olefins: epoxidation, dihydroxylation and aminohydroxylation. 3. Reduction of olefins: asymmetric hydrogenation. 4. Reduction of ketones and imines 5. Asymmetric C-C bond formation: nucleophilic attack on carbonyls, imines and enones 6. Asymmetric transition metal catalysis in C-C bond forming reactions (cross-couplings, Heck reactions, allylic substitution, carbenoid reactions) 7. Chiral Lewis acid catalysis (aldol reactions, cycloadditions, Mannich reactions, allylations) 1 Catalytic Asymmetric Synthesis - Lecture 1 Background and general principles • Why asymmetric synthesis? The need to prepare pharmaceuticals and other fine chemicals as single enantiomers drives the field of asymmetric synthesis.
    [Show full text]
  • A Review on Chiral Chromatography and Its Application to the Pharmaceutical Industry
    Chemsearch Journal 2(1): 8 - 11 Publication of Chemical Society of Nigeria, Kano Chapter CHIRAL CHROMATOGRAPHY AND ITS APPLICATION TO THE PHARMACEUTICAL INDUSTRY: A REVIEW Mudi, S. Y. and *Muhammad, A. Department of Pure and Industrial Chemistry, Bayero University, PMB 3011, Kano. *Correspondence author: [email protected] ABSTRACT Chiral chromatographic enantioseparation has been in practice by researchers. There has been a considerable interest in the synthesis and separation of enantiomers of organic compounds especially because of their importance in the biochemical and pharmaceutical industries. Often, these compounds are purified rather than being produced by chiral-specific synthesis. We herein present a general discussion that focuses on the chromatographic enantioseparation, which we hope will be useful to chromatographic and pharmaceutical industries. Keywords: Chiral chromatography, enantioseparation, pharmaceutical industry. INTRODUCTION giving differing affinities between the analytes Chromatography is the collective term for a set of (Schreier et al., 1995). laboratory techniques for the separation of mixtures. It The main goal of this review is to provide a brief involves passing a mixture dissolved in a "mobile overview of chiral separations to researchers who phase" through a “stationary phase”, which separates are versed in the area of analytical separations but the analyte from other compounds in the mixture unfamiliar with chiral separations. This review based on differential partitioning between the mobile highlights significant issues of the chiral and stationary phases. Subtle differences in a separations and provides salient examples from compound's partition coefficient result in differential specific classes of chiral selectors where retention on the stationary phase and thus effecting appropriate. the separation (Laurence and Christopher, 1989; Pascal et al., 2000).
    [Show full text]