PREPARATION OF (+)-CATECHIN, (-)-EPICATECHIN, (-)-CATECHIN, (+)-EPICATECHIN, AND THEIR 5,7,3',4'-TETRA-O-BENZYL ANALOGUES

Processes for preparing racemic mixtures of 5,7,3',4'-tetra-O-benzyl-(~)- catechin and (~)-epicatechin involves (i) condensing 2-hydroxy-4,6- bis(benzyloxy)-acetophenone and 3,4-bis(benzyloxy)benzaldehyde, cyclizing th e resulting compound, oxidizing the resulting compound; (ii) dihydroxylating ( E)- 3-(3',4'-bis(benzyloxy)phenyl)prop-2-ene-1 -ol and reducing the 1 ,2-diol; o r (iii) coupling 3,5-bis(benzyloxy)phenol with (~)-3,5-bis(benzyloxy)-2-(3',4' - bis(benzyloxy)phenyl)allyl)phenol and cyclizing the resulting chalcone. A process for preparing the benzylated epimers of catechin and epicatechin involves seven steps. 3,4-Bis(benzyloxy)benzaldehyde is coupled with 2-hydro xy- 4,6-benzyloxy-acetophenone to form a chalcone. The chalcone is selectively reduced to an alkene. The phenolic group of the alkene is protected. The protected alkene is asymetrically dihydroxylated. The resulting compound is deprotected, cyclized, and finally hydrolyzed. Epimers resulting from these processes are chemically resolved or separated by chiral high pressure liqui d chromatography. Also disclosed is a method for preparing enantiomerically pu re 5,7,3',4'-tetra-O-benzyl-(+)-catechin from a racemic mixture using dibenzoyl -L- tartaric acid monomethyl ester. Further, disclosed is an improved process fo r preparing dibenzoyl-L-tartaric acid monomethyl ester.