Selective inhibition of R-enzymes by simple organic acids in yeast-catalysed reduction of ethyl 3-oxobutanoate

To achieve high enantiomeric excess in Bakers' yeast reduction of ethyl 3-oxobutanoate (2) to ethyl (S)-(+)-3-hydroxybutanoate(1), selective inhibition of unnecessary R-enzymes by organic acids, their derivatives and sulfhydryl reagents have been widely investigated. Acetic acid and crotonic acid were identified as good ee controllers, both giving alcohol (1) in up to ≥99% ee. Some other alkenoic and alkanoic acids with short side chains were found to be effective but to lesser degrees. Sulfhydryl reagents were ineffective or in some cases had the opposite effect to what was intended. The pH alone of the reaction mixture had no relation to the resulting high values of enantiomeric excess. The result that the effect of acetic acid on yeast reduction was not dependent on the preincubation time strongly suggested that the inhibition was a noncovalent one.

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