Total Synthesis of Resvebassianol A, a Metabolite of Resveratrol by Beauveria bassiana.

Abstract

Resveratrol is a well-known dietary polyphenol because it has a variety of beneficial biological activities. The fungus Beauveria bassiana is one of the most frequently used microorganisms for the biotransformation of polyphenols. Recently, resvebassianol A (2), a glycosylated metabolite of resveratrol by B. bassiana, was isolated and structurally elucidated. It was demonstrated to exhibit antioxidant, regenerative, and anti-inflammatory activities with no cytotoxicity. Here, we report the first total synthesis of resvebassianol A, 4′-O-β-(4‴-O-methylglucopyranosyl)resveratrol (2), and its regiomer, 3-O-β-(4‴-O-methylglucopyranosyl)resveratrol (3). Key reactions include (i) the construction of a stilbene core via a novel Heck reaction of aryl halides and styrenes, and (ii) glycosylation with unnatural methylglucopyranosyl bromide. The glycosylation step was carefully optimized by varying the bases and solvents. Resveratrol metabolites 2 and 3 were obtained at 7.5% and 6.3% of the overall yield, respectively.