Biomimetic Synthesis of Meroterpenoids by Dearomatization-Driven Polycyclization

Abstract

A biomimetic route to farnesyl pyrophosphate and dimethyl orsellinic acid (DMOA)-derived meroterpenoid scaffolds has yet to be reported despite great interest from the chemistry and biomedical research communities. A concise synthetic route with the potential to access DMOA-derived meroterpenoids is highly desirable to create a library of related compounds. Herein, we report novel dearomatization methodology followed by polyene cyclization to access DMOA-derived meroterpenoid frameworks in six steps from commercially available starting materials. Furthermore, several farnesyl alkene substrates were used to generate structurally novel, DMOA-derived meroterpenoid derivatives. DFT calculations combined with experimentation provided a rationale for the observed thermodynamic distribution of polycyclization products.

Keywords: 3,5-dimethylorsellinic acid; biosynthesis; dearomatization; meroterpenoids; polyene cyclization.