Taichi Hojima, Shingo Komeda, Yusuke Higashino, Masahiro Hamada, Noriyuki Nakajima, Takashi Kawasaki and Akiko Saito
Flavan-3-ol derivatives are common plant-derived bioactive compounds with strong various biological activities. In particular, (–)-epigallocatechin-3-O-gallate exhibits a variety of moderate biological activities without severe toxicity. Its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. In general, the galloyl moieties of flavan-3-ol derivatives are thought to be essential to their strong biological activities. However, it is not clear which position is most effective for modification with the galloyl moiety to strengthen the biological activities because various galloylated analogs are difficult to obtain in pure form in a quantity large enough for assays. Therefore, we synthesized various galloylated flavan-3-ol derivatives in a stereoselective and regioselective manner. We reported in a previous paper that 3,5-digalloyl-(–)-epicatechin displayed much stronger inhibitory activity than 3,5-digalloyl-(+)-catechin did against HeLa S3 cell proliferation. In this study, we describe synthetic studies of 7-galloyl- and 3,7-digalloyl-modified (–)-epicatechin and (+)-catechin and compared their biological activities, HeLa S3 cell proliferation inhibitory activity and DPPH radical scavenging activity with those of 3,5- digalloyl- (–)-epicatechin. The results indicated that 3,7-digalloyl derivative did not inhibit HeLa S3 cell proliferation. Furthermore, 3,5-digalloyl- (–)-epigallocatechin was synthesized to evaluate the importance of the number of phenolic hydroxyl groups on the B-ring. Contrary to our expectations, 3,5-digalloyl-(–)-epigallocatechin exhibited a weaker inhibition of HeLa S3 cell proliferation than 3,5-digalloyl- (–)-epicatechin did. The DPPH radical scavenging activity of the synthesized compounds suggested that the galloyl-modified position and the number of phenolic hydroxyl groups on B-ring affected to the radical scavenging ability. In conclusion, we found that 3,5-digalloyl-(–)-epicatechin exhibited a superlative HeLa S3 cell proliferation inhibitory effect among the galloylated flavan-3-ol derivatives we synthesized and DPPH radical scavenging activity was affected by the galloyl-moiety-introduced position and the number of phenolic hydroxyl groups on the B-ring.
