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