Enantioselective biocatalytic reduction of 2,2-disubstituted ethylacetoacetates: an indirect desymmetrization approach for the synthesis of enantiopure (S)-4-hydroxy-3,3-disubstituted pentane-2-ones

Abstract

Ethyl 2,2-disubstituted-3-oxobutanoates were biocatalytically reduced to the corresponding (S)-ethyl 3-hydroxy-2,2-disubstitutedbutanoate with the growing cells of Klebsiella pneumoniae (NBRC 3319) with excellent enantioselection. The biocatalytically derived enantiopure hydroxyl esters were then synthetically manipulated to give (S)-4-hydroxy-3,3-disubstituted pentane-2-ones. The whole process can be regarded as an indirect enantioselective enzymatic desymmetrization method for the synthesis of (S)-4-hydroxy-3,3-disubstituted pentane-2-ones.