An improved synthesis of procyanidin dimers:: Regio- and stereocontrol of the interflavan bond

A direct and general synthesis of procyanidin dimers B1, B2, B3 and B4 (10a-d) is presented. The approach is based on the stoichiometric coupling of two protected monomeric units (the nucleophilic 2a-b and electrophilic 4a-b partners) and deals with the regio- and stereocontrol of the C4-C8 interflavan bond as well as the control of the degree of oligomerization. The synthesis involves a five-step pathway starting from the native catechin (1a) or epicatechin (1b) to the fully deprotected dimers 10a-d. Furthermore, the process appears to be iterative as the coupling intermediates 9a-d themselves can be readily used in further selective syntheses of trimers or higher oligomers.