Resveratrol Synthesis

The biologically active compound (trans)-resveratrol was synthesized in 45.4% overall yield, via a seven step synthetic route. Methyl ester of 3,5-dihydroxy benzoic acid was prepared from 3,5-dihydroxy benzoic acid and methanol in 98% yield. The reaction of the ester with benzyl chloride followed by reduction with LiAlH₄ gave 3,5-bis(benzyloxy)benzyl alcohol. The alcohol was then bromated with PBr₃ to give the key intermediate 3,5-bis(benzyloxy) benzyl bromide, which reacted with triethylphosphite to give diethyl- [3,5-bis(benzyloxy)benzyl] phosphonate. Then the product was condensed with anisaldehyde to give (E)-1-[3,5-bis(benzyloxy)phenyl] -2-[4-methoxyphenyl]ethene. The final compound resveratrol was obtained by deprotection of benxyl and methyl groups with BBr₃/CH₂Cl₂.Reaction of 4-(benzyloxy) benzaldehyde instead of the anisaldehyde with diethyl-[3,5-bis(benzyloxy)benzyl] phosphonate gave only trans isomer3,4',5-tri(benzyloxy)stilbene. Deprotection of the benzyl groups with BBr₃/CH₂Cl₂ gave resveratrol in 50% overall yield, or with AlCl₃ also gave the final compound resveratrol in 47.6% overall yield.