Enzymes in Organic Synthesis. 24. Preparations of Enantiomerically Pure Chiral Lactones via Stereospecific Horse Liver Alcohol Dehydrogenase Catalyzed Oxidations of Monocyclic Meso Diols

Article abstract of DOI:10.1021/ja00381a024

Preparative-scale horse liver alcohol dehydrogenase catalyzed oxidation of monocyclic meso diols provides a direct and convenient one-step route to a broad range of chiral γ-lactones of value as synthons in asymmetric synthesis.The general applicability of the method is demonstrated by oxidations of cis-1,2-bis(hydroxymethyl) substrates of the cyclohexyl, cyclohexenyl, cyclopentyl, cyclobutyl, cyclopropyl, and dimethylcyclopropyl series.For each diol, oxidation of the hydroxymethyl group attached to the S chiral center occurs exclusively, and the pure γ-lactone products are isolated in high (68-90percent) yields and of 100percent ee.In contrast, the enzyme does not exhibit significant enantiomeric selectivity in its catalysis of oxidations of the corresponding racemic trans diols.The stereospecificities observed, or lack thereof, are as predicted by the active-site model.