Synthesis of the staurosporine aglycon

New Synthetic Approach to Arcyriaflavin-A and Unsymmetrical Analogs

“…12 It involves an intramolecular cycloaddition process between alkyne and pyranoindolone residues, followed by a formal nitrene insertion. A similar route has recently been reported, starting from a methyl pyridazino [4,5-b]indole-4-carboxylate.…”

“…22 The carbazole 7a, readily obtained by DDQ aromatization, was then heated in triethyl phosphite for 2 h, producing final E-ring closure via formal nitrene insertion. 11,12 After chromatography, the pure arcyriaflavin-A analogue 8a was obtained in 55% yield. 23 In order to ascertain whether this methodology could also be used to prepare arcyriaflavin-A (8b) and analogs with -NH-in the D-ring, our next target was the synthesis of this natural product.…”

“…11,12 Our route is outlined in Scheme 1 below, and is based on a Diels-Alder reaction between maleimides and 1-(2-nitrophenyl)-3-trialkylsiloxy-1,3-butadienes as first part of the synthetic strategy, followed by a Fischer indolization with phenylhydrazine or p-substituted derivatives, aromatization and nitrene E-ring closure.…”

Total (Bio)Synthesis: Strategies of Nature and of Chemists

“…A particularly creative synthesis was presented by the research group of Moody, who aimed to use no protecting groups on the nitrogens [10]. All atoms of the staurosporine aglycone scaffold were incorporated from the beginning by condensation of 142 , in turn derived from aldehyde 143 by formal reductive amination (58% yield), with 144 and oxalyl chloride to give 145 in 76% yield.…”

“…Final cyclization to give the product 1 was achieved by treatment of 148 with triethyl phosphite (54% yield) (Fig. 26a) [10]. The only sense in which this strategy relates to a biosynthetic route is that all carbons and nitrogens present in the final structure are derived from an early coupling reaction.…”