Asymmetric total synthesis of crinipellin B

Abstract

Crinipellins is only one group of natural product having a tetraquinane framework and isolated from the culture broth of the basidomycete Crinipellis stipitaria . Crinipellin B is one of crinipellins and has biological activity. Although there have been a lot of synthetic approaches to crinipellin B, there has been only one report of the total synthesis of crinipellin B in racemic form. The intramolecular cycloaddition reaction of 1,3-trimethylenemethane(TMM)diyl was successfully utilized in construction of tetraquinane core structure and could be generated from allene and N-toluenesulfonylhydrazone For asymmetric synthesis of crinipellins, chiral resolution or induction methodology furnished highly enantiomerically pure chiral intermediate, and Sharpless epoxidation set up the other stereocenters favored epoxide for cycloaddition. Preparation of tetraquinane structure of Crinipellin B with proper stereochemistry was succeeded through TMM diyl cycloaddition reaction, and further functional group modification furnished the formal total synthesis of crinipellin B as the synthesis lead to the Pier’s intermediate in his total synthesis of crinipellin B. The enantioselective total synthesis fo crinipellin B was accomplished through modified sequence of reactions in Piers’s synthesis from the cycloaddition reaction product to the natural product.