Chiral Pool

3 Key excerpts on "Chiral Pool"

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  eBook - ePub

  Asymmetric Synthesis of Drugs and Natural Products

  • Ahindra Nag(Author)
  • 2018(Publication Date)
  • CRC Press

    (Publisher)

  1 Basic Stereochemical Approaches to Natural Products and Drugs Ahindra Nag

  CONTENTS 1.1Basic Concept of Chirality 1.2Meso Compounds 1.3Tautomerism and Valance Tautomerism 1.4Conformation 1.5Fischer Projection and Absolute Configuration 1.6Chiral Resolution 1.6.1Crystal Picking 1.6.2Chemical Separation 1.6.3Biochemical Separation 1.6.4Chromatographic Separation 1.7Application of Enantiomers in Drugs and Natural Products Problems Answers References

  1.1Basic Concept of Chirality

  An asymmetric carbon atom (known as the stereogenic center) is attached to four different groups1 termed a chiral (pronounced as kiral). The word chiral derives from the Greek word cheira meaning hand, which is closely related to optical activity. For a molecule to have chirality, it must not possess a plane, a center, or a fourfold alternating axis of symmetry. Molecules which are mirror images of each other are termed enantiomers (from the Greek entatios meaning opposite) and need chiral recognition to be separated. Enantiomers react1 , 2 , 3 , 4 , 5 , 6 at different rates with other chiral compounds and may have different solubilities in the presence of an optically active solvent. They may display different absorption spectra under circulatory polarized light. Enantiomers may have different optical rotations, which could be either (+), that is, dextrorotatory (clockwise), or (−), that is, levorotatory (anticlockwise), and can be determined by a polarimeter. The optical purity of a mixture of enantiomers is given by

  % Optical purity of sample = 100 ∗

  Specific rotation of sample

  Specific rotation of a pure enantiomer

  Specific rotation

  α D

  =

  α obs

  /c l

  where

  αobs is the experimentally observed rotation

  c is the concentration in g/mL

  l is the path length of the cell used, expressed in dm (=10 cm)

  Enantiomeric excess

  7

  is one of the indicators of the success of an asymmetric synthesis. The enantiomeric excess (eep

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  eBook - ePub

  Chiral Drugs

  • Cynthia Challener, Cynthia A Challener(Authors)
  • 2017(Publication Date)
  • Routledge

    (Publisher)

  PART I CHIRALITY Passage contains an image CHAPTER 1 OVERVIEW OF CHIRALITY

  The existence of optical isomerism has been known since its discovery in 1815 by the French chemist Jean-Baptiste Biot.1 However, it was only in the early twentieth century that Cushny2 established the relevance of chirality to the pharmaceutical industry by showing that one enantiomer of hyoscyamine possessed greater pharmacological activity than the other.

  Today, most new drugs and those under development consist of a single optically active isomer, and chirality is also becoming an issue for the agrochemical industry. Regulatory agencies throughout the world are currently reviewing the importance of chirality with regard to pharmaceutical and agrochemical products. New guidelines from agencies such as these have been key drivers for the focus on single enantiomer products in these industries. Optically pure compounds also have roles in electronics, foods, and flavor and fragrance products.

  The “Chiral Pool” of readily available, relatively inexpensive chiral compounds has been expanding at a rapid rate as more and more products are produced in large quantities at economic prices. New developments in technologies for isolating, preparing, and purifying chiral materials have greatly increased the opportunities for utilizing optically pure compounds in commercial applications. Novel techniques for classical resolution, new methodologies for developing selective enzymes for biocatalysis, advances in the application of microorganisms for chemical production, and continued progress in the area of asymmetric synthesis have all contributed to the growth of this field.

  Definition of Chirality Superimposability

  Chiral molecules are molecules whose mirror images are not superimposable upon one another. Conversely, achiral compounds

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  eBook - PDF

  Practical Process Research and Development

  • Neal G. Anderson(Author)
  • 2000(Publication Date)
  • Academic Press

    (Publisher)

  There are four basic approaches, shown in Table 16.2 [14]. A few examples and some perspective are worthwhile. II.A. Products from Fermentation and the Chiral Pool Fermentation has produced natural products such as antibiotics and the cholesterol-lowering agents pravastatin and lovastatin. Modification of fermentation products has led to semisynthetic compounds such as simvastatin (see Figure 1.2), peni-cillins, and cephalosporins. With increased capability in genetic engineering, 330 16. Chiral Syntheses TABLE 16.2. Approaches for Producing Enantiomerically and Diastereomerically Pure Products • Fermentation: isolation of natural and unnatural products • Chiral carbon pool: preparation of intermediates • Separating racemates Preferential crystallization of one enantiomer (occurs for conglomerates, not true racemic crystals) Kinetic resolution (enzymatic and nonenzymatic) Crystallization of diastereomeric compounds (salts and covalent modifications) • Asymmetric synthesis Stoichiometric Catalytic microbial strains are producing higher yields of fermentation products, and unnat-ural products are also being made [15, 16]. The Chiral Pool has provided the backbone of many products. Carbohydrates [17] and amino acids are often used because of the high degree of functionality and the ready availability of these compounds from natural sources. Enalapril maleate contains the dipeptide L-alanyl-L-proline (Figure 16.1a) [18]. Aztreonam is derived from L-threonine (Figure 16.1b) [19]. The chiral ester 2 was prepared from an amino acid derivative 1 (Figure 16.1c) [20]. In this transformation the original chiral center from L-cysteine was destroyed, similar to self-immolative processes [21].

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