Rebeccamycin aglycone

Howard-Jones AR, Walsh CT (2006) Staurosporine and Rebeccamycin Aglycones Are Assembled by the Oxidative Action of StaP, StaC, and RebC on Chromopyrrolic Acid. J Am Chem Soc 128 12289... 

The indole[2,3-a]carbazole 185 possessing the rebeccamycin aglycone unit [122-132,135,136] was synthesized from the reaction of N-methyl-maleimide and 2,2/-bisindolyl 181 via Michael type addition. In the presence of aluminum trichloride, the bisindole reacts to form the Michael adducts 182 and 183. The mono-Michael adduct 182 was dehydrogenated in the presence of Pd/C in a one pot procedure to produce 184 and 185 (Scheme 43) [ 137]. 

The exact nature of the intermediates and the reactions between IPA or its 7-chloro derivative and rebeccamycin aglycone was unknown at that time, but a pathway including the condensation of two tryptophan-derived units, several oxidations, and... 

Independently, in 1998, the Cordell (290,379,380) and Pearce (381) groups published some preliminary biosynthetic results on staurosporine and rebeccamycin, typical representative members of the indolo[2,3-fl]pyrrolo[3,4-c]carbazole alkaloids. Cordell s biosynthetic studies on staurosporine were based on feeding experiments with L-tryptophan. These studies showed that two units of L-tryptophan, with the two carbon side-chains intact, were responsible for the biosynthesis of staurosporine aglycone. Further experimental studies are necessary to establish the nature of the intermediate in the biotransformation of L-tryptophan to staurosporine. Although these studies are not complete, they gave for the first time insight into the biosynthesis of staurosporine (379,380). 

The biosynthesis of 1 follows a pattern seen for all bisindoles that have been biosynthetically investigated thus far [17, 163, 164] two molecules of L-tryptophan (123) are oxidized and then dimerized to give an initial bisindole skeleton (Fig. 24). Historically, the biosynthesis of staurosporine (121) has been investigated in parallel with that of rebeccamycin (124), a related bisindole. Both molecules are thought to be biosynthesized through nearly identical routes to give the aglycone... 

As shown in Scheme 36, a Heck polyannulation reaction was realized between dibromo(indolyl)maleimide 209 and diacetylenyl trifluoroacetanilide 210 to assemble indolo[2.3-a]carbazole 211, the Af-prolecied aglycone of rebeccamycin (25). Four bonds were formed in one step from a single monocyclic 1,3-diacetylene precursor [101] and the trifluoroacetyl protecting groups were readily cleaved during the workup. 

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