The proanthocyanidins are known as condensed tannins and/or oligomeric flavonoids, in which flavan-3-ol units are linked together by carbon-carbon bonds from the 4-position of one unit to the 8-position of the next unit. Many biological activities, powerful antioxidant activity, free-radical-scavenging activity and an anti-tumor-promoting effect, have been reported for flavonoids and their investigation is now increasingly important. Proanthocyanidins have been obtained from many kinds of plants, but because they are usually obtained as a complex mixture of structurally related compounds, it is very difficult to isolate them in a pure form. Consequently, we planned to develop efficient synthetic methods leading to procyanidins with a high level of purity and stereoselectivity. We previously described TMSOTf-catalyzed intermolecular condensation achieved high levels of 3,4-trans condensation in excellent isolation yields to synthesize procyanidin dimers. We report here in detail TMSOTf-catalyzed intramolecular dimer synthesis. Although intramolecular condensation of catechin-catechin units afforded 3,4-cis dimers selectively, condensation of catechin-epicatechin, epicatechin-catechin and epicatechin-epicatechin gave 3,4-trans dimers. The trimer synthesis with intramolecular condensation methdod is now underway. And we also report stereoselective synthetic studies of eight trimers with intermolecular condensation method. Monomer electrophiles reacted with dimer nucleophiles in the presence of TMSOTf and afforded the corresponding trimers. Catechin trimer and epicatechin-epicatechin-catechin trimer were synthesized in good yields with this method. However, when catechin-epicatechin dimer was used as a nucleophile, the TMSOTf-catalyzed condensation with catechin or epicatechin electrophile did not proceed at all. The inhibitory activity of Maillard reaction was tested using catechin 1, epicatechin 2, synthesized procyanidin oligomers, their methylated and acetylated compounds. As a result, phenolic and their acetylated compounds inhibited the Maillard reaction strongly, but methylated compounds had no inhibitory activity.
