Staurosporine aglycon

The cyclized products 393 can be prepared by the intramolecular coupling of diphenyl ether or diphenylamine(333,334]. The reaction has been applied to the synthesis of an alkaloid 394[335]. The intramolecular coupling of benzoyl-A-methylindole affords 5-methyl-5,10-dihydroindenol[l,2-b]indol-10-one (395) in 60% yield in AcOH[336]. Staurosporine aglycone (396) was prepared by the intramolecular coupling of an indole ring[337]. 

The Michael addition of the carbanions derived from esters to nitroalkenes followed by reductive cycLizadon has been used extensively for the preparation of pyrrondin-3-ones fEq 1076 This strategy is used for synthesis of the carbaaole alkaloid staurosporine aglycon CK-352c ... 

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). 

Oxidative homocoupling of aromatic and heteroaromatic rings proceeds with Pd(OAc)2 in AcOH. Biphenyl (165) is prepared by the oxidative coupling of benzene [104,105], The reaction is accelerated by the addition of perchloric acid. Biphenyl-tetracarboxylic acid (169), used for polyimide synthesis, is produced from dimethyl phthalate (168) commercially [106], Intramolecular coupling of the indole rings 170 is useful for the synthesis of staurosporine aglycone 171 [107]. 

Fig. 25 A sample of synthetic routes (a-c) to the staurosporine aglycone (I) with biomimetic features ...

Synthetic studies on indolocarbazoles Total synthesis cf staurosporine aglycon... 

Mohankrishnan et al s)mthesized staurosporine aglycon and its analogues with 28-36% overall yield, using 2-methylindole (110) as synthetic precursor [50]. The key steps for the s)mthesis of indolocarbazole alkaloids involved electrocychzation and nitrene insertion reactions as depicted in Schemes 16 and 17. 

Synthesis ofpyrrolidin-2-ones and staurosporine aglycon (K-252c) by intermolecular Michael reaction... 

Rajeshwaran GG, Mohanakrishnan AK. S3mthetic studies on indolocarbazoles Total synthesis of staurosporine aglycon. Qrg. Lett. 2011 13 (6) 1418-1421. 

Mahboobi S, Eibler E, Roller M, Kumar KCS, Popp A. S)mthesis of p3rrrohdin-2-ones and of staurosporine aglycon (K-252c) by intermolecular Michael reaction. J. Oig. Chem. 1999 64 4697- 4704. 

Burkhard S, Winterfeld E. Reactions with indole derivatives, XLVIII. A simple s)m-thesis of the staurosporine aglycon. Heterocycles 1983 20 469-476. 

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