Stereocontrol in Bakers' Yeast Reduction Leading to Natural Product Synthesis

Stereocontrol in bakers' yeast reduction can be achieved by introduction of a sulfur functional group into substrates. α-Methylthio-β-keto esters are reduced to give exclusively (3S)-3-hydroxy esters. α-Substituted β-keto thiol esters and dithioesters afford (2R,3S)-3-hydroxy esters with high diastereo-and enantioselectivity. Ketones possessing 1,3-dithiane, phenylsulfenyl, or phenylsulfonyl groups at the α-position are transformed also into the corresponding (S)-secondary alcohols. Optically pure (S)-(phenylsulfinyl)acetones can be obtained by kinetic resolution of racemic derivatives with the yeast. Diastereo- and enantioselective reduction of 1,2-diketones leading into (1S,2S)-1,2-diol derivatives can be also achieved by introduction of 1,3-dithiane, phenylsulfenyl or phenylsulfonyl groups into the α-position. Reductions of carbon-carbon double bond of sulfur-functionalized prenyl derivatives provide both chiral (R)- and (S)-C5-building blocks for terpenoid synthesis. The utility of the reduction products as chiral building blocks is demonstrated in the synthesis of biologically active natural products such as pheromones, sugars, antibiotics etc. by functional group transformation and carbon-carbon bond formation reactions with the aid of sulfur functional groups.