Carbazole alkaloids biological sources

In the present review, we summarize the occurrence, biogenesis, biological activity, and the chemistry of carbazole alkaloids, which have been classified based on their natural sources, ring system, and substitution pattern. While a comprehensive overview is given on all carbazole alkaloids isolated from natural sources, only their total syntheses published since 1990 are discussed. 

The bis-carbazole alkaloids contain previously known monomeric carbazoles as structural subunits. All bis-carbazole alkaloids were isolated only from plants of the genus Murray a, until 1996, when clausenamine-A (203) (see Scheme 2.48) was isolated from the stem bark of C. excavata. The plant M. euchrestifolia is one of the richest sources of carbazole alkaloids. The bis-carbazoles often co-occur with monomeric carbazoles in the root bark, stem bark, and leaves of this plant (3,5-7,158,159). The aspect of atropisomerism for axially chiral, bis-carbazoles was considered only recently. Thus, in many cases it is not clear whether the isolated natural products are racemic or enantiomerically pure. Moreover, little attention has been paid to the relationship between their stereochemistry and biological activity. 

A number of dimeric carbazole alkaloids have been isolated from various natural sources in recent years, which have been found to exhibit various biological activities including antitumor, anti-inflammatory, and cytotoxic activities. In 1996, clausenamine A was isolated from the stem and root bark of Clausena excavata, which is used in Chinese herbal medicine for detoxification treatment following poisonous snakebites. The first total synthesis of clau-... 

A broad structural variety of carbazole alkaloids vdth useful biological activities has been isolated from different natural sources. The pharmacological potential of this class of natural products led to the development of diverse methods for the synthesis of carbazoies [29,30]. We elaborated an efficient iron-mediated construction of the carbazole framework by consecutive C-C and C-N bond formation. This method provides highly convergent routes to carbazoies as demonstrated first for 4-deoxycarbazomycin B (Scheme 15.8) [31]. 

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. 

The majority of indolocarbazole alkaloids, isolated so far from nature, are derivatives of the indolo[2,3-fl]pyrrolo[3,4-c]carbazole ring system 292. They have been isolated from soil organisms, slime molds, and marine sources (3,7,8,252-255), and have shown a broad range of potent biological activities, such as antifungal, antimicrobial, antitumor, and antihypertensive activity (3,7,256-260,267-270). Their activity as potent inhibitors of protein kinase C (PKC) has received special attention, and was the focus of several investigations (8,257,258,271-280). The history of these natural products dates back about 30 years (Scheme 2.73). 

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