Attempted synthesis of 3-hydroxy-2-octadecylindole. Proposed structural revision of previously prepared 3-hydroxy-2-octadecylindole and a proposed structure of fistulosin

作者：Clawson Ronald W Jr; Dacko Christopher A; Deavers Robert E III; Akhmedov Novruz G; Soderberg Bjorn C G^*

来源：Tetrahedron, 2009, 65(43): 8786-8793.

DOI：10.1016/j.tet.2009.08.055

• Palladium-catalyzed
• Indoles
• Reductive-annulation
• Fistulosin

A synthetic route to 3-hydroxy-2-octadecylindole, the putative structure of the novel indole alkaloid fistulosin, starting from 2-nitro-1-iodobenzene was examined. Key steps include formation of a 1-stannyl-substituted 1-methoxy-1-alkene from a Fischer chromium carbene, intermolecular Kosugi-Migita-Stille coupling, and a palladium-catalyzed reductive N-heteroannulation. Demethylation of 3-methoxy-2-octadecylindole, a possible immediate precursor to 3-hydroxy-2-octadecylindole, was unsuccessful and gave instead methyl 2-(1-oxononadecanyl)aminobenzoate. The structure of the isolated alkaloid was suggested to be 2-(1-oxooctaclecanyl)aminobenzoate by comparison of analytical data with a synthetic sample. In addition. oxidation of 2-octadecylindole gave a 2,2'-dimer, a compound identical to previously prepared 3-hydroxy-2-octadecylindole.

• 出版日期2009-10-24