Diastereomers

10 Key excerpts on "Diastereomers"

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  eBook - ePub

  Smith and Williams' Introduction to the Principles of Drug Design and Action

  • H. John Smith, Hywel Williams(Authors)
  • 2005(Publication Date)
  • CRC Press

    (Publisher)

  Biological environments at a molecular level are highly chiral being composed of chiral biopolymers, e.g. proteins, glycolipids and polynucleotides, from the chiral building blocks of L-amino acids and the D-carbohydrates. As nature has made a preference in terms of its stereochemistry it is not surprising that enzymes and receptor systems show a stereochemical preference for one of a pair of stereoisomers. The interaction of a drug with a receptor, or enzyme active site, involves interaction between the functionalities of the drug molecule and complementary sites or groups on the receptor. Such interactions may have considerable steric constraints in terms of interatomic distance and steric bulk between such functionalities. In the case of stereoisomers the three dimensional spatial arrangement of the functionalities is of considerable significance.

  Enantioselectivity in drug action should not be surprising as many of the natural ligands are themselves chiral, e.g. neurotransmitters, autocoids, hormones, endogenous opioids etc. Indeed Lehmann has stated that “the stereoselectivity displayed by pharmacological systems constitutes the best evidence that receptors exist and that they incorporate concrete molecular entities as integral components of their active sites”.

  4.2 DEFINITIONS AND NOMENCLATURE

  Stereochemistry is concerned with the three dimensional spatial arrangement of the atoms within a molecule. The prefix stereo originating from the Greek stereos meaning solid or volume. Stereoisomers are compounds which differ only in the three-dimensional arrangement of their constituent atoms in space and such isomers may be divided into two groups namely enantiomers and diastereoisomers. Enantiomers are pairs of compounds which are non-superimposable mirror images of one another and in terms of physicochemical properties, differ only in their ability to rotate the plane of plane polarised light which is equal in magnitude but opposite in direction. Such isomers are said to be chiral (from the Greek chiros meaning handed) and are variously referred to as optical isomers or enantiomorphs (Greek enantios opposite, morph

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  eBook - ePub

  Stereochemistry and Stereoselective Synthesis

  An Introduction

  • Mihály Nógrádi, László Poppe, József Nagy, Gábor Hornyánszky, Zoltán Boros(Authors)
  • 2016(Publication Date)
  • Wiley-VCH

    (Publisher)

  14
• Enantiomer: one among those nonsuperposable stereoisomers that are related as mirror images (enantiomers thus form pairs of mirror images). Enantiomers must be chiral. Scalar physical properties of enantiomers are identical; they only differ in vectorial physical properties, such as optical rotation. Their chemical behavior toward achiral agents is identical, while it may differ toward chiral agents [2–4].
  [This definition is in accord with IUPAC recommendation [2–4] on stereochemistry stating that enantiomers are pairs of molecular entities, which are not superposable and are related as mirror images.]15
Figure 2.6
Possible forms of isomerism.
Conformation/configuration and isomeric relationships are illustrated by the isomers of cyclohexane (C6 H12 ) (Figure 2.7 ). It follows from the definitions and examples in Figure 2.7 that it depends on the type of isomerism under which conditions components of a mixture of isomers can be separated. Constitutional isomers and Diastereomers are differing in most of their chemical and physical properties, while enantiomers can only be differentiated by direction-dependent (vectorial) properties and exhibit different chemical reactivities only toward chiral partners. Examples in Figure 2.7 well illustrate the necessity of giving exact definitions and justify taking into consideration the criterion of isolability.
Figure 2.7
Conformation, configuration, and various types of isomerism. The molecules shown all have the same molecular formula (C6 H12 ). Molecules placed into a common box are either identical (≡) or exist as a set of conformations capable to interconversion ( ). (c.i.: constitutional isomers; D: Diastereomers; and E: enantiomers).
By the example of cyclohexane shown in Figure 2.7 , it can be seen that its different conformational states cannot be isolated and are not separable molecular entities. Here, the imprecision of the IUPAC definition of conformation becomes apparent since the three states differ not only by rotation around single bonds. In the chair and the half-chair conformations, C–C–C bond angles are also different. The two states of methylcyclopentane shown are related as mirror images, but these are superposable and therefore achiral