Synthesis of valuable chiral intermediates by isolated ketoreductases:: Application in the synthesis of α-alkyl-β-hydroxy ketones and 1,3-diols

Regio- and stereoselective reductions of alpha-substituted 1,3-diketones to the corresponding beta-keto alcohols or 1,3-diols by using commercially available ketoreductases (KREDs) are described. A number of alpha-monoalkyl- or dialkyl-substituted symmetrical as well as non-symmetrical diketones were reduced in high optical purities and chemical yields, in one or two enzymatic reduction steps. In most cases, two or even three out of the four possible diastereorners of alpha-alkyl-beta-keto alcohols were synthesized by using different enzymes, and in two examples both ketones were reduced to the 1,3-diol. By replacing the alpha-alkyl substituent with the OAc group, 1-keto-2,3-diols, as well as 1,2,3-triols were synthesized in high optical purities. These enzymatic reactions provide a simple, highly stereoselective and quantitative method for the synthesis of different diastereomers of valuable chiral synthons from nonchiral, easily accessible 1,3-diketones.