Migrastatin and Dorrigocins Are Shunt Metabolites of Iso-Migrastatin

摘要

Migrastation(1)has emerged as a novel natural product lead for anticancer drug discovery because of its potent inhibitory effect on human tumor cell migration.Dorrigocin A(2)and B(3)were described as the first natural product inhibitors of the carboxyl methyltransferase involved in the processing of Ras-related proteins,serving as a valuable tool to study cellular signal transduction.Here we report that neither 1 nor 2 and 3 are bona fide natural products but shunt metabolites of iso-migrastatin(4).These findings shed new light into the stability,stereochemistry,and biosynthetic relationship of this family of metabolites and should now be taken into consideration in evaluating their biological activities.