9-Oxygenated tricyclic carbazole alkaloids

Scheme 1 1-Oxygenated and 2-oxygenated tricyclic carbazole alkaloids...

In contrast to the 1- and 2-oxygenated tricyclic carbazole alkaloids, most of the 3-oxygenated and the 3,4-dioxygenated tricyclic carbazole alkaloids were isolated from Streptomyces (Scheme 2). Their common structural feature is a 2-methylcarbazole, although biosynthetic studies on carbazomycin B have shown that tryptophan is the precursor of the carbazole nucleus [26]. 4-De-... 

For the quinone imine cyclization of iron complexes to carbazoles the arylamine is chemoselectively oxidized to a quinone imine before the cyclodehydrogenation [99]. The basic strategy of this approach is demonstrated for the total synthesis of the 3-oxygenated tricyclic carbazole alkaloids 4-deoxycarbazomycin B, hyellazole, carazostatin, and 0-methylcarazostatin (Scheme 17). 

Despite many applications of the iron-mediated carbazole synthesis, the access to 2-oxygenated tricyclic carbazole alkaloids using this method is limited due to the moderate yields for the oxidative cyclization [88,90]. In this respect, the molybdenum-mediated oxidative coupling of an arylamine and cyclohexene 2a represents a complementary method. The construction of the carbazole framework is achieved by consecutive molybdenum-mediated C-C and C-N bond formation. The cationic molybdenum complex, required for the electrophilic aromatic substitution, is easily prepared (Scheme 23). 

Scheme 25 Synthesis of the 2-oxygenated tricyclic carbazole alkaloids 66-69 and l,r-bis(2-hydroxy-3-methylcarbazole) 70...

While 1- and 2-oxygenated tricyclic carbazole alkaloids were isolated primarily from higher plants, various tricyclic carbazole alkaloids, which are 3-oxygenated or 3,4-dioxygenated, were obtained from alternative natural sources, such as microbial, marine, and mammalian sources. 

A. Tricyclic Carbazole Alkaloids 1 3-Oxygenated Tricyclic Carbazole Alkaloids... 

Although a large number of 2-oxygenated tricyclic carbazole alkaloids have been isolated from different natural sources, only a few syntheses of this class of alkaloids were reported. This is mainly due to the lack of general methods, as well as the difficulty associated with the known synthetic methods, to build up the required substitution pattern. Prior to 1990, some total syntheses of 2-oxygenated carbazoles were reported and were covered in the earlier treatises by Kapil (1), Husson (2), and Chakraborty (3) in Volumes 13, 26, and 44 of this series. Since 1990, the only total syntheses which appeared in the literature for this class of carbazole alkaloids were transition metal-mediated or -catalyzed approaches, respectively. These general approaches offered a series of 2-oxygenated carbazole alkaloids (8,10). 

Our palladium-catalyzed approach for the construction of the carbazole framework led to the 6-oxygenated tricyclic carbazole alkaloids glycozoline (128), methyl 6-methoxycarbazole-3-carboxylate (133), glycomaurrol (135) and micromeline (130), as well as to the furo[2,3-c]carbazole alkaloid eustifoline-D (132) (Scheme 29) [149]. Palladium-catalyzed coupling of p-bromoanisole (125) and p-toluidine (126) as the first step led almost quantitatively to the diarylamine 127. Oxidative cyclization of intermediate 127 using 0.1 equiv. of palladium(ll) acetate in the presence of an excess of copper(ll) acetate provided glycozoline... 

This section includes the carbazole alkaloids that have substitutions and functionalizations without any further heterocyclic fusions and annulations on the 9H-carbazole nucleus. Further, irrespective of their natural sources, based on the oxygenated substitution pattern, these tricyclic carbazole alkaloids were classified into the following sub-sections. 

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