New Approach for the Synthesis and Isolation of Dimeric Procyanidins

A semisynthetic approach for the strategic formation of various procyanidins has been developed. Procyanidin-rich grape seed extracts were reacted with flavan-3-ols under acid catalysis. The reaction enables the formation of dimeric procyanidins and the elimination of higher oligomeric and polymeric procyanidins through degradation. An easy and fast method for the isolation of large amounts of procyanidins after semisynthetic formation by high-speed countercurrent chromatography is presented. Dimeric procyanidins (B1, B2, B3, B4, B5, and B7) were obtained and isolated. Furthermore, galloylated dimeric procyanidins [(−)-epicatechin-3-O-gallate-4β→8-(+)-catechin, (−)-epicatechin-3-O-gallate-4β→8-(−)-epicatechin, (−)-epicatechin-3-O-gallate-4β→6-(−)-epicatechin, and (−)-epicatechin-4β→8-(−)-epicatechin-3-O-gallate], as well as trimeric procyanidins [C1, (−)-epicatechin-4β→6-(−)-epicatechin-4β→8-(−)-epicatechin, and (−)-epicatechin-4β→6-(−)-epicatechin-4β→6-(+)-catechin] were obtained and isolated as side products. This approach also afforded gambiriins A1 and A2, which were all isolated and unambiguously identified, and the novel 3-(2,4,6-trihydroxyphenyl)-1-(3,4-dihydroxyphenyl)-propan-2-ol-1β→8-(−)-epicatechin (gambiriin A4).