Enzymes in Organic Synthesis. 27. Horse Liver Alcohol Dehydrogenase Catalyzed Oxidoreductions of 3-Alkylthiopyran Ketones and Alcohols

Article abstract of DOI:10.1021/jo00154a007

The stereospecificity of horse liver alcohol dehydrogenase (HLADH) toward S-heterocyclic substrates has been studied further.While 3-methyl- and 3-ethyltetrahydrothiopyran-4-ones (1) and -4-ols (2,3) are not good substrates, the ketones 1 and trans alcohols 3 do undergo highly stereoselective enzyme-mediated oxidoreductions in preparative-scale (up to 2 g of substrate) reactions.In contrast, HLADH-catalyzed oxidations of the cis alcohols 2 are too slow to be preparatively viable.Reductions of the racemic ketones 1 occur with high enantiomeric- and stereoselectivity,with the 3S enantiomers being converted in excellent yields to the corresponding 3S,4S trans alcohols 3 of 78-90 percent ee.The unreactive 3R ketone enantiomers of 58-66 percent ee are recovered from the same reactions.Oxidations of the racemic trans alcohols 3 are also markedly stereoselective, permitting the unreactive (3R,4R)-3 enantiomers of 65-85 percent ee to be isolated in good yields.