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.
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doi: 10.1039/C5QO00416K