SYNTHESIS OF THE STAUROSPORINE AGLYCON

A short synthesis of the staurosporine aglycon (6) is reported, the indolocarbazole skeleton being constructed by an intramolecular Diels-Alder reaction followed by a nitrene-mediated ring closure. The synthesis starts by acylation of ethyl indole-2-acetate with oxalyl chloride. The resulting indole-3-glyoxalyl chloride is quenched with 2-nitrocinnamylamine (29) to give the amide (31). Hydrolysis of the ester group and cyclodehydration then gives the pyranoindolone (35). On heating in bromobenzene, the pyranoindolone 35 undergoes intramolecular Diels-Alder reaction to give, after loss of carbon dioxide and air oxidation, the carbazole 36, which on treatment with triethyl phosphite cyclizes to the staurosporine aglycon. The overall yield from ethyl indole-2-acetate is 22.6%.