Ellagitannin Chemistry. The First Synthesis of Dehydrohexahydroxydiphenoate Esters from Oxidative Coupling of Unetherified Methyl Gallate

A simple o -chloranil-mediated oxidative dimerization of methyl gallate in anhydrous ether furnishes a dimethyl dehydrohexahydroxydiphenoate (DHHDP) product as a pale yellow precipitate in good yield. This methyl gallate dehydrodimer rapidly rearranges in acetone to give a mixture of two additional DHHDP regioisomers. One of these species corresponds to the isomer of the dehydrohexahydroxydiphenoyl group commonly observed in dehydroellagitannin natural products. Sodium dithionite-mediated reduction of the initially formed dimethyl dehydrohexahydroxydiphenoate and/or its derived regioisomers efficiently furnishes dimethyl hexahydroxydiphenoate (HHDP). Addition of N -(carbobenzyloxy)- l -cysteine benzyl ester to dimethyl dehydrohexahydroxydiphenoate(s) in THF solution produces two diastereomeric 3- S -cysteinyl derivatives of dimethyl hexahydroxydiphenoate.