Total Synthesis of (-)-Vescalagin, the Iconic Member of the C-Glucosidic Ellagitannin Family

The first total synthesis of the 2,3,5-O-(S,R)-NonaHydroxyTriPhenoylated (NHTP) and 4,6-O-(S)-HexaHydroxy-DiPhenoylated (HHDP) C-glucosidic ellagitannin (-)-vescalagin was accomplished through a bioinspired route involving intramolecular atroposelective cupric-diamine complex-mediated phenolic couplings of gallates to forge its HHDP and NHTP units and a methoxyamine-driven opening of a glucopyranose intermediate followed by a phenolic aldol-type reaction to form its C-arylglucosidic bond. The minor epimer that resulted from this bond-forming event was used to complete also a first total synthesis of the vescalagin epimer, (-)-castalagin.