Arcyriarubin synthesis

Hill et al. reported an efficient short synthesis of staurosporinone (293) using a palladium-mediated oxidative cyclization of the bisindolylmaleimide arcyriarubin A (349) as the key step (766). The key intermediate, arcyriarubin A (349), was prepared... 

Faul et al. reported an improved synthesis of arcyriarubin A (349) by reaction of indolylmagnesium bromide (1358) with dichloromaleimide (1366). Following Hill s route, 349 was transformed to staurosporinone (293) in three steps and 47% overall yield (see Scheme 5.225). This approach provides, so far, the shortest access to staurosporinone (293) with the best overall yield (771) (Scheme 5.228). 

Uang et al. reported a synthesis of staurosporinone (293) starting from arcyriarubin A (349). Oxidative photocyclization of bisindolylmaleimide 349 in the presence of a catalytic amount of iodine in THF/acetonitrile led to arcyriaflavin A (345) in 85% yield. Finally, using modified Clemmensen reduction conditions, arcyriaflavin A (345) was transformed to staurosporinone (293) in 68% yield (795) (Scheme 5.254). 

The structures of these bisindole maleimides were confirmed by synthesis. The reaction of indolyl magnesium bromide (10) with 2,3-dibromo-A -methylmaleimide (11) in toluene led to bisindolylmaleimide (12), which was converted into arcyriarubin A (6) through alkaline hydrolysis followed by heating with ammonium acetate (Scheme 1). The reaction of 10 and 11 in THF yielded monosubstitution product (13) which after protection of the indole NH group with the Boc residue was used to prepare unsymmetrically substituted bisindolylmaleimide, arcyriarubin B (1) [8]. 

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