Stereochemical specificity

The diene addition is stereochemically specific (22). Although two stereoisomers are possible, the endo and the exo forms, in the addition of maleic anhydride to CPD the endo adduct is the exclusive product (23). 

For drug substances and drug products, applications for enantiomers and racemates should include a stereochemically specific identity test and/or a stereochemically selective assay. The choice of control tests should be based on the method of manufacture and stability characteristics and, in the case of the finished product, its composition. 

The main discussion of mechanism has been centred around the stereochemical specificity of the fission, particularly with respect to the role of cyclic intermediates... 

Stereochemical specificity, in which the enzyme catalyzes reactions of only one stereoisomer of a compound. 

When a racemic substance is hydrogenated or when the reduction leads to the production of centers of asymmetry, the phytochemical reduction will take at first a completely or partially asymmetric course. Examples of such asymmetric reactions are the conversions of pure racemic valeraldehyde, acetaldol, furoin and furil, diacetyl and acetyl-methylcarbinol to optically active alcohols. Occasionally meso forms also arise, as for example in the case off glycols (p. 84). The reasons for the stereochemical specificity of these reactions have not been clarified. This type of phenomenon has frequently been observed in the related intramolecular dismutation of keto aldehydes, especially if enzyme materials of differing origins are used. 

Since drugs interact with optically active, asymmetric biological macromolecules such as proteins, polynucleotides, or glycolipids acting as receptors, many of them exhibit stereochemical specificity. This means that there is a difference in action between stereoisomers of the same compound, with one isomer showing pharmacological activity while the other is more or less inactive. In 1860, Louis Pasteur was the first to demonstrate that molds and yeasts can differentiate between (+)- and (-)-tartarates, utilizing only one of the two isomers. 

Transketolase catalyzes the reversible transfer of a hydroxyacetyl fragment from a ketose to an aldehyde. Because the ketose products formed by transketolase reactions are not acceptors for a consecutive transformation by the same enzyme, we have investigated the option to include a xylose (glucose) isomerase (Xyll E.C. 5.3.1.5), which has similar stereochemical specificity, for ketose to aldose equilibration (Scheme 2.2.5.13). Starting from racemic lactaldehyde 32a, the transketolase forms 5-deoxy-D-xylulose 35a, which indeed was accepted by the Xyll in situ for diastereospecific conversion into 5-deoxy-D-xylose 36a. The latter again proved to be a substrate of transketolase which completed a tandem operation to furnish 7-deoxy-sedoheptulose 37a as the sole bisadduct in 24% overall yield and in enantio- and diastereomerically pure quality [35, 36]. All four stereocenters of the resulting product are completely controlled by the enzymes during this one-pot operation. The procedure profits from the limited tolerance of the isomerase... 

Problem 21.51 Account for the stereochemical specificity of enzymes with chiral substrates. 

Erzyme Cbenzyme Stereochemical specificity for ricotinamde ring (AorBt Extpagc(s)... 

Liquid-Liquid Microheterogeneous Reaction Systems. Several authors have shown that liquid-liquid microheterogeneous reaction systems may be advantageous for overall chemical yield and positional and stereochemical specificity of photochemical reactions [22]. Ionic interphases may for instance assist in differentiating between reactive intermediates and thus enhance reaction specificity and chemical yield. 

Define chiral, enantomer, diastereomer, epimer, anomer (see Chapter 4), prochiral (see Chapter 9). What is meant by the statement that biochemical reactions are stereochemically specific Why is such stereospecificity to be expected in organisms (which are constructed from asymmetric units) See Chapter 9 for further discussion. 

Stereochemical specificity was demonstrated with cyclohexane oxide (Eq. D2G), which opens with Walden inversion to give trans i-... 

Alexander and Dittmer 0 have secured evidence of perceptible stereochemical specificity in the isomerization of cis- and trans-2,2-epoxybutane with phosphoric acid as catalyst. Although the cw-isomer... 

Stereochemical specificity fe manifest in the reaction of frans-2,3-epoxybutane with acetic acid, which Wjiustein and Lucas reported to give only ryJAre-2-acetoxy-3-butanol (Eq. 746). Hydrolysis leads to optically inactiveme o-2,3-hutanediol. Similarly, Bdeeeken and Cohen1 had described previously the preparation of racemic [Pg.460]

Another exploitation of stereochemically specific deuterium labeling at C(3) was exemplified in an approach to determine the relative one-center epimerization rate constants in a cis-1 -cyano-2-isobutenylcyclopropane. Thanks to the deuterium labeling (equation 3) the distinction could be made without resort to chiral compounds, and the k. k2 ratio was found to be (3.9 0.5) 1 at 206.7 °Cl6tl. 

The stereochemical specificity of enzymes depends on the existence of at least three different points of interaction, each of which must have a binding or catalytic function. A catalytic site on the molecule is known as an active site or active centre of the enzyme. Such sites constitute only a small proportion of the total volume of the enzyme and are located on or near the surface. The active site is usually a very complex physico-chemical space, creating micro-environments in which the binding and catalytic areas can be found. The forces operating at the active site can involve charge, hydrophobicity, hydrogen-bonding and redox processes. The determinants of specificity are thus very complex but are founded on the primary, secondary and tertiary structures of proteins (see Appendix 5.1). 

More recently the stereochemically specific reduction of cyclopro-pene to cyclopropane and, in acid solution, to propylene has been demonstrated for the molybdothiol systems (288). This also parallels nitrogenase behavior. 

Further progress on the problem of the stereochemical specificity of cyclitol oxidation by A. suboxydans will depend on the isolation of the enzyme or enzymes involved. Cell-free preparations capable of oxidizing wn/o-inositol have been obtained,43 44 but these have not been further purified. The enzyme is apparently a true dehydrogenase, since it can couple with diaphorase.44... 

Morse, D. E., Hooker, N., and Duncan, H., GABA induces metamorphosis in Haliotis, V stereochemical specificity, Brain Res. Bull., Suppl. 2, 5, 381, 1980. 

The stereochemical specificity of taste receptor proteins capable of combining with carbohydrate molecules and of translating the message into sweet sensation is investigated by Jakinovich using a sophisticated neurophysiological technique. 

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