An Improved Synthesis of Procyanidin Dimers: Regio‐ and Stereocontrol of the Interflavan Bond

Abstract 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)