The Total Synthesis of Asbestinin-6

University Of California Irvine, Irvine CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Asbestinin-6 was isolated from Briareum asbestinum of the order (Gorgonacea. Although the absolute stereochemistry has not been established for any member of the asbestinin family of natural products, it is thought to be related biosynthetically to the cladiellins, which have established structures. The asbestinins have been shown to have strong antitumor, antimicrobial activity, and exhibit histamine and acetylcholine antagonism. The asbestinins have similar cyclic skeletons which contain a stereochemically complex hexahydroisobenzofuran ring. The key step of this proposed synthesis of asbestinin-6 will focus on the formation of this ring in a stereoselective fashion by further optimization of the Prins-pinacol methodology previously reported by the Overman group. Other key steps will include the formation of a nine member ring system through olefin metathesis, and the formation of a seven member cyclic ether. Upon completion of the first total synthesis of asbestinin-6 it is anticipated that several objectives will be achieved. These objectives include: 1) development of a general method to access structurally similar biologically active compounds; 2) further investigation into biological activity; and 3) determination of the absolute stereochemistry of asbestinin-6.