Catalytic Asymmetric Synthesis of Biologically Active Molecules

Based on the concept of bifunctional asymmetric catalysis, chiral ligands containing a carbohydrate scaffold were designed. Rare earth metal complexes of the ligands produced general and practical catalytic enantioselective cyanation of ketones and ketoimines. Structural studies of the asymmetric catalysts revealed that the active catalysts are polymetallic complexes containing higher-order structures. The higher-order structure determines the function (activity and enantioselectivity) of the catalysts. The thus-developed catalytic enantioselective methods for the synthesis of tetrasubstituted carbons were applied to the synthesis of biologically active molecules. Catalytic asymmetric synthesis of fostriecin and its analog, lactacystin, Tamiflu®, and garsubellin A are described.