Staurosporine indolocarbazole alkaloids

Strategies Towards the Synthesis of Staurosporine Indolocarbazole Alkaloid and Its Analogues... 

The earliest application of inverse-detected 2D NMR techniques to a terrestrial alkaloid of which we are aware was the assignment of the H and NMR spectra of the indolocarbazole alkaloid staurosporine (7) reported by Meksuriyeri and Cordell (1988). Later in 1988, Edwards et al. utilized HMQC in the elucidation of the structure of pumiliotoxin-A (10) and related indolizine alkaloids isolated from Panamanian poison frogs. These were the only applications of inverse-detected 2D NMR techniques in alkaloid to appear in 1988. We will thus begin with staurosporine (7) and proceed to related carbazole-based alkaloids before continuing to pumiliotoxin-A (10) and other terrestrial alkaloids. 

Recently still another class of compounds of fused carbazole alkaloids has been recognized. Two particulary interesting members of this class are staurosporine (8a) and its aglycon (8b), both potent inhibitors of protein kinase C. The chemistry of the indolocarbazole alkaloids ha recently been thouroughly reviewed " and will therefore not be discussed in this treatise. 

Only a few methodologies have been developed for S3mthesizing complex carbohydrate intermediates for use in the total s)mthesis of indolocarbazole alkaloids such as staurosporine (1). Some of those strategies are summarized in the succeeding sections ... 

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. 

In a related but different vein, the cytochrome P450 enzyme StaP (CYP245A1) catalyzes a putative diradical coupling reaction involving one-electron oxidation of each of two indole rings to form the indolocarbazole alkaloid skeleton of staurosporine and rebeccamycin (Fig. 4.40) [230, 231]. The crystal stractuie of the protein-sub-... 

In 2013, the complex indolocarbazole alkaloid staurosporine (4) was employed as a model compound by Senior et al. [29] to evaluate the abibty of the 1ADEQUATE experiment to probe long-range carbon—carbon coupling pathways as a supplement to more traditional HMBC data in severely proton-deficient molecules. It was also interesting to note that while not all of the Jcc correlations were observed in the conventional 1,1-ADEQUATE spectrum, there were a number of the missing correlations that were observed in the dual-optimized inverted Jcc. l. -ADEQUATE spectrum that was also acquired for the sample. 

The interest in indolocarbazoles began in the early 1950s with the first rational synthetic approaches. Since then, this interest has escalated dramatically as numerous derivatives of indolo[2,3-a]carbazole (1) have been isolated from various natural sources. These derivatives were demonstrated to possess highly potent and diverse biological effects, prompting novel efforts in the area. In particular, derivatives of indolo[2,3-n]pyrrolo[3,4-c]carbazole, such as the alkaloid staurosporine (8), have attracted much attention. 

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