Stereoinversion mechanism

Although the mechanism of stereoinversion is not yet clear, the - - mechanism widely accepted for the stereoisomerization of allylpalladium derivatives cannot operate in this case, since the concerted - - mechanism should be accompanied by a stereoinversion of the second double bond, which has not been observed. The observed inversion of only the bromine-bearing C=C bond may involve a dipolar mechanism shown in Scheme 397. This mechanism needs to be experimentally supported, however. 

Figure 7.12. Mechanism for the stereoinversion of (S)- to (R)-mandelate catalyzed by mandelate racemase [10],...

Figure 7.14. The thiol template mechanism for the stereoinversion of l-to D-phenylalanine catalyzed by phenylalanine racemase [54].

The thiol-template mechanism is utilized in other enzymes involved in production of peptide-based antibiotics. Actinomycin synthetase II (ACMSII) and b-L-(a-aminoadipolyl)-L-cysteinyl-D-valine (ACV) synthetase catalyze the stereoinversion of valine residues vithin peptide-based antibiotics, and employ ATP and the PAN cofactor in a mechanism similar to that depicted in Fig. 7.14 [58, 59]. ACMSII catalyzes the stereoinversion of a valine within the tripeptide 4-MHA-L-Thr-D-Val (MHA, 4-methyl-3-hydroxyanthranilic acid), which is a precursor for the antibiotic actinomycin D. ACV synthetase catalyzes the stereoinversion of the valine within ACV, which is a precursor for penicillin and cephalosporin [60-63]. ACV synthetase has been shown to have much broader substrate specificity, also accepting non-natural substrates [64, 65]. 

Figure 7.16. Mechanism for the stereoinversion of L- to D-proline catalyzed by proline racemase (upper manifold) and water catalyzed proton exchange of the free enzyme (lower manifold).

There are a number of cofactor independent carbohydrate epimerases that act on activated substrates, such as keto-sugars and keto-sugar nucleotides, although there is a paucity of details about their mechanisms. D-ribulose-5-phosphate 3-epimerase catalyzes the stereoinversion of substrate about the C-3 carbon to form D-xylulose 5-phosphate (as in Fig. 7.15) [102, 103]. Solvent hydron is completely incorporated into the product at the C-3 carbon, during epimerization in the d-xylulose 5-phosphate to o-ribulose 5-phosphate direction [102], This was taken as evidence for a two-base mechanism. 

Polymerization mechanism Microstructure with isolated stereoinversion triad/triad and pentad/pentad relationships... 

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