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

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