Stereochemically specific hydrogenation

Like Thr 124 and Thr 215, the Asn 69 and Asn 159 residues occupy equivalent positions in the two homologous motifs of TBP. By analogy with the symmetric binding of a dimeric repressor molecule to a palindromic sequence described in Chapter 8, the two motifs of TBP form symmetric sequence-specific hydrogen bonds to the quasi-palindromic DNA sequence at the center of the TATA box. The consensus TATA-box sequence has an A-T base pair at position 4, but either a T-A or an A-T base pair at the symmetry-related position 5, and the sequence is, therefore, not strictly palindromic. However, the hydrogen bonds in the minor groove can be formed equally well to an A-T base pair or to a T-A base pair, because 02 of thymine and N3 of adenine occupy nearly stereochemically equivalent positions, and it is sufficient, therefore, for the consensus sequence of the TATA box to be quasi-palindromic. 

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. 

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). 

The observation of MCM-catalyzed hydrogen exchange between substrates and C5 of adenosylcobalamin predated the earliest evidence of radicals in coenzyme Bi2-dependent reactions. Early evidence for the participation of free radicals included the observation of a breakdown in stereochemical specificity in the reaction of the substrate analogue ethylmalonyl-CoA. The weakness of the Co-C5 bond and observation of... 

The mechanism of the reaction is not clear, but the enzyme reacts in presence of O2 and yields the a-keto acid, ammonia, and hydrogen peroxide. In spite of the restricted stereochemical specificity, the specificity for the amino acids is rather broad. The affinity of the monoamine oxidase is low for short-chain amino acids, but the enzyme is very effective on intermediate and long-chain amino acids. The enzyme attacks straight- and branched-chain amino acids, as well as amino acids containing aromatic ringlike phenylalanine, epinephrine, etc. 

In the course of the catalytic hydrogenation of a,us dinitriles over Raney nickel, by-products are obtained from C-N and C-C bond formation. The mechanism of the formation of these compounds was investigated. Cyclic and linear secondary amines can result from the same secondary imine through a transimination process involving a ring-chain tautomerism. Stereochemical results for 2-aminomethyl-cyclopentylamine (AMCPA) are in accordance with a specific cyclisation pathway favored by an intramolecular hydrogen bond giving rise to the cis isomer from aminocapro-nitrile, unfavored in the case of adiponitrile which leads to the trans AMCPA as the major isomer. 

The last stereochemically cryptic feature of this transformation concerns the specificity of the enzyme for the diastereotopic hydrogen atoms at C-l of 1,2-propanediol. To resolve this point Zagalak et al. [18] prepared ( R,2R)- and (1 R,2S)-1,2-[ 1 -2H,]propanediols (12 and 13) by reducing (R) and (5)-lactaldehydes with (4/ )-[4-2H,]NADH and liver alcohol dehydrogenase (Fig. 9). The cyclic acetals of 12 and 13, formed from nitrobenzaldehyde, gave different H-NMR spectra, and their configurations were determined by spectral comparison [20] with racemic reference compounds of known (relative) configuration. 

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