Asymmetric Synthesis of cis -3α-Aryloctahydroindole Alkaloids by Ene-Reductase Dehydrocyclization

In this study, an unprecedented, enzymatic, and enantioselective desymmetrization and cyclization reaction of achiral 4,4-disubstituted cyclohexanones has been developed for the asymmetric synthesis of cis-3α-aryloctahydroindole alkaloids bearing an all-carbon quaternary stereocenter as well as a tertiary carbon stereocenter. Using different ene-reductases as the biocatalysts, a variety of 3α-aryloctahydroindoles have been obtained in high yields (71-90%) and excellent enantioselectivities (>99% ee), providing an efficient strategy to prepare these important alkaloids.