Convergent Assembly of the Tetracyclic Meroterpenoid (-)-Cyclosmenospongine by a Non-Biomimetic Polyene Cyclization.

Abstract

The cationic cyclization of polyenes constitutes a powerful and elegant transformation, which has been utilized by nature's biosynthetic machinery for the construction of complex polycyclic terpenoids. Previous studies by chemists to mimic this cyclization in the laboratory were limited to different modes of activation using biosynthetic-like precursors, which accommodate only simple methyl-derived substituents. Here we describe the development of an unprecedented and highly efficient polyene cyclization of an aryl enol ether containing substrate. The cyclization was shown to proceed in a stepwise manner to generate three rings and three consecutive stereocenters, two of which are tetrasubstituted, in a single flask. The developed transformation is of great synthetic value and has enabled the convergent assembly of the tetracyclic meroterpenoid (-)-cyclosmenospongine.