Enantioselective Organocatalytic Michael/Aldol Sequence: Anticancer Natural Product (+)-trans-Dihydrolycoricidine

A total synthesis of the anticancer natural product (+)-trans-dihydrolycoricidine is reported from alpha-azidoacetone and cinnamaldehyde precursors. Key elements include an asymmetric organocatalytic sequence proceeding by a regio-specific secondary-amine-catalyzed syn Michael addition followed by an intramolecular aldol reaction. The sequence results in the formation of an advanced intermediate, containing three stereogenic centers, in one step which and was converted into the title compound in eight steps.