Chromopyrrolic acid

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... 

Another example of a partially biomimetic strategy is shown in Fig. 25b. Here the analogy is to the starting materials two indole-containing molecules, 136 and 137, which were dimerized via formation of the same bond as seen in the reaction carried out by StaD on two molecules of indole-3-pyruvic acid imine (125). This bond - between the (3-carbons of the L-tryptophan precursor (123) - once formed biosynthetically leads to 127, which spontaneously forms chromopyrrolic acid (128) in oxygen (Fig. 24). In the biosynthetic route, this reaction is between two unactivated carbons, which would seem to render it challenging, although low levels of 128 formation are seen between indole-3-acetic acid, L-tryptophan, and... 

Overall, the biosynthesis of 160 is characterized by the dimerization of 168 to give the central structure of the molecule. This head-to-tail dimerization strategy is efficient, using the same substrate twice, and is a sensible route, given the existence of the shikimate pathway, which provides, in turn, a precursor to 168. An analogous dimerization route can be seen for the biosynthesis of K252c (1), described in Sect. 5, where two molecules of indole-3-pyruvic acid imine (125), derived in turn from L-tryptophan (123), are dimerized to give an intermediate that leads to chromopyrrolic acid (128). In both cases, the monomer precursors, either 168 or 125, serve as both nucleophiles and electrophiles, and are activated to react by the presence of the appropriate enzymes. 

Hoshino et al. described that in cultures of Chromobacterium violaceum, lycogalic acid (35, = chromopyrrolic acid) was derived from tryptophan [18]. It was therefore assumed that lycogalic acid (35) was formed by oxidative dimerization of 3-(indol-3-yl)pyruvic acid followed by reaction of the resulting 1,4-dicarbonyl intermediate with an equivalent of ammonia. On the basis of this idea, lycogarubin C (33) was synthesized from methyl 3-(indol-3-yl)pyruvate (37) in a simple one-pot process (Scheme 4). 

Figure 5.51 Proposed mechanism for the formation of chromopyrrolic acid.

Wang Y, Chen H, Makino M, Shiro Y, Nagano S, Asamizu S, Onaka H, Shaik S (2009) Theoretical and experimental studies of the conversion of chromopyrrolic acid to an antitumor derivative by cytochrome P450 StaP the catalytic role of water molecules. J Am Chem Soc 131 6748-6762... 

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