Enantioselective Synthesis of Flavonoids

Abstract

Enantiopure (scalemic) flavonoid monomers such as permethoxylated chalcone epoxides and dihydroflavonols are available via HPLC resolution of the racemates using a Chiralpack OT( +) column. Depending on the oxygenation pattern, epoxy chalcones can also be prepared in enantiomeric purity up to 96 percent by the utilization of synthetic poly(peptide) or cinchona alkaloid catalyzed epoxidation with hydrogen peroxide, aqueous sodium hypochlorite, or tert-butyl hydroperoxide. Transformation of these oxiranes into dihydroflavonols and ultimately flavan-3,4-diols without 'loss' in optical purity is possible by treatment with hydrogen chloride in absolute methanol, followed by sodium borohydride reduction. Direct catalytic hydrogenation of the epoxides leads to a-hydroxydihydrochalcones of comparable enantiomeric purity that can be used for determination of the absolute configuration of naturally occurring analogues by comparison of CD data.