3,3',5'-Tri-O-Methylpiceatannol and 4,3',5'-Tri-O-Methylpiceatannol: Impróvements over Piceatannol in Bioactivity

Abstract

Piceatannol (3,4,3'',5''-tetrahydroxy-trans-stilbene) [1] (NSC 365798) has recently been isolated and was subsequently synthesized for NCI tumor panel testing as a new antileukemic natural product from the seeds of Euphorbia lagascae. During the synthesis, a bioactive reaction mixture of several partially O-methylated piceatannol analogues was obtained. This mixture has now been maximized and subjected to bioactivity-directed fractionation, using brine shrimp lethality, to yield, 3,3'',5''-tri-O-methylpiceatannol [5] (NSC 381281); this new compound has improved stability and better bioactivity in several systems than piceatannol itself. To confirm the structure, 5 was synthesized from vanillin [2]. In addition, the isovanillin [3] analogue, 4,3'',5''-tri-O-methylpiceatannol [6] (NSC 381864), another new compound, was synthesized and found to be bioactive.