Various processes are disclosed for preparing protected epicatechin oligomers having (4β,8)-interflavan linkages. In one process, a
tetra-O-protected epicatechin
monomer or
oligomer is coupled with a protected, C-4 activated epicatechin
monomer in the presence of an acidic clay such as a mortmorillonite clay. In another process, a 5,7,3′,4′-benzyl protected or a 3-acetyl-, 5,7,3′,4′-benzyl protected epicatechin or
catechin monomer or
oligomer is reacted with 3-O-acetyl-4-[(2-benzothiazolyl)
thio]-5,7,3′,4′-
tetra-O-benzylepicatechin in the presence of
silver tetrafluoroborate. In another process, two 5,7,3′,4′-benzyl protected epicatechin monomers activated with 2-(benzothiazolyl)
thio groups at the C-4 positions are cross-coupled in the presence of silver tetrofluoroborate. A process is also disclosed for reacting an unprotected epicatechin or
catechin monomer with 4-(benzylthio)epicatechin or
catechin. The use of naturally-derived and synthetically-prepared procyanidin (4β,8)4-pentamers to treat
cancer is also disclosed.