A concise total synthesis of sespenine, a structurally unusual indole terpenoid from Streptomyces.

Sun Y, Meng Z, Chen P, Zhang D, Baunach M, Hertweck C, Li A (2016) A concise total synthesis of sespenine, a structurally unusual indole terpenoid from Streptomyces. Org Chem Front 3, 368-374. PDF Supplement

Abstract

Sespenine is a structurally unusual indole sesquiterpenoid isolated from endophytic Streptomyces sp. HKI0595. Herein, we report a ten-step (the longest linear sequence) synthesis of this molecule from commercially available materials, on the basis of our first generation synthesis. Sharpless asymmetric epoxidation and Stille−Miyata coupling were used to construct a functionalized epoxy ester, which underwent Ti(III) mediated reductive radical cyclization to give a trans-decalin intermediate with a 2-methoxycarbonylindole side chain. Oxidation of this compound afforded a pair of epimeric 3-hydroxyindolenines, and the major isomer entered a bioinspired cascade of Prins cyclization/Friedel−Crafts/retro Friedel−Crafts under acidic conditions, to furnish the polycyclic core of sespenine. Sespenine analogues bearing different C2 substituents were prepared with similar chemistry. Xiamycin A, a carbazole congener of sespenine, was synthesized from the minor hydroxyindolenine epimer as well.

Involved Units and Groups
HKI-Authors
Identifier

doi: 10.1039/C5QO00416K