SYNTHESIS AND ANTI-HEPATITIS C VIRUS ACTIVITY OF GALLIC ACID DERIVATIVES WITH CHIRAL CENTER

Abstract

Objective: In this work, we aim to synthesize gallic acid derivatives with chiral center and to evaluate its anti-hepatitis C virus (anti-HCV) activity.Methods: Synthesis of the target derivatives was started from esterification of commercially available boc deprotection (Boc)-L-threonine with allyl bromide, followed by Boc with HCl/EtOAc, amidation, and Sharpless asymmetric dihydroxylation with (DHQ)2PHAL or (DHQD)2PHAL as a ligand to give desired gallic acid derivatives. The synthesized gallic acid derivatives were then evaluated for anti-HCV activity and cytotoxicity.Results: The target derivatives were successfully synthesized in ranging from 20% to 30% of yield. Anti-HCV activity of the derivatives is greatly improved by the presence of chiral center, hydroxyl group, and monomethoxy group on the aromatic ring, with showed no cytotoxicity. This fact revealed that the chiral center, hydroxyl group, and monomethoxy group on the aromatic ring of gallic acid derivatives are responsible for its anti-HCV activity. Moreover, gallic acid derivative which possesses a chiral center of bottom facial stereochemistry was found to have a stronger anti-HCV activity than gallic acid derivative with chiral center of top facial stereochemistry. Suggesting that, bottom facial stereocenter in gallic acid derivative was more effective for anti-HCV activity than the top facial stereocenter.Conclusion: Gallic acid derivatives with chiral center exhibited a greater antiviral activity against HCV than gallic acid. Thus, the derivatives should be considered as a promising candidate for the treatment of HCV infection.