Carbazoles 7-oxygenated

When N,A/ -dimethyl-Af,N -diphenyl-p-phenylenediamine (231) underwent irradiation in die presence of oxygen, a remarkably regioselective reaction was observed, from which the /V,A/ -dimediylindolo[2,3-f ]carbazole (190) was obtained, without coformation of die other possible isomeric product, indolo[3,2-/)]carbazole (4). The expected intermediate 232, where only one ring closure had taken place, could not be detected. The authors attributed this fact to a two-photon autosensitization mechanism in which die conversion of 231 into 190 is sensitized by 232, permitting accumulation of 232 only in extremely small concentrations (83JA6268). 

The Pschorr reaction also works with substrates containing a bridge other than oxygen. Thus various tricyclic products containing a biaryl subunit are accessible, e.g. carbazoles and fluorenes. 

Nojiri H, J-W Nam, M Kosaka, K-I Morii, T Takemura, K Furihata, H Yamane, T Omori (1999) Diverse oxygenations catalyzed by carbazole l,9a-dioxygenase from Pseudomonas sp. strain CA 10. J Bacterial 181 3105-3113. 

The oxygen transfer to the -acetylenic carbon results in the very intense benzoyl cation, whereas the transfer to the a-carbon, via a series of fragments corresponding to the loss of OH , CO and CO2, respectively, leads to annelated heterocycles such as the radical cation of carbazole, as a result of elimination of CO81. The generation of the benzoyl cation was rationalized as shown in Scheme 1281. 

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-... 

The reaction of the complex salt 6a with the arylamine 12 affords by regio-selective electrophilic substitution the iron complex 13 [88] (Scheme 11). The oxidative cyclization of complex 13 with very active manganese dioxide provides directly mukonine 14, which by ester cleavage was converted to mukoeic acid 15 [89]. Further applications of the iron-mediated construction of the carbazole framework to the synthesis of 1-oxygenated carbazole alkaloids include murrayanine, koenoline, and murrayafoline A [89]. 

The iron-mediated synthesis of 2-oxygenated carbazole alkaloids is limited and provides only a moderate yield (11%) for the oxidative cyclization to 2-methoxy-3-methylcarbazole using iodine in pyridine as the reagent [90]. Ferricenium hexafluorophosphate is the superior reagent for the iron-mediated arylamine cyclization leading to 3-oxygenated carbazoles (Scheme 12). Electrophilic substitution of the arylamines 16 with the complex salt 6a leads to the iron complexes 17. Oxidative cyclization of the complexes 17 with an excess of ferricenium hexafluorophosphate in the presence of sodium carbonate affords... 

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...

Rutaceae family (11) have a one-carbon-substituent at position 3 of the carbazole nucleus and an oxygen substituent at position 1 or 2. The structure of these alkaloids can vary from simple substituted carbazoles to molecules containing complex terpene moieties. 

Among the large number of carbazole alkaloids that have been isolated from M. koenigii are also many 2-oxygenated derivatives. In 1985, Bhattacharyya et al. isolated 2-methoxy-3-methylcarbazole (37) from the petroleum ether extract of the seeds of M. koenigii (55). The UV spectrum (Tmax 235,255,300, and 328 nm) and the IR... 

Since 1966, several carbazole alkaloids which are oxygenated at the C-iing were isolated from different natural sources. Glycozoline (86) was the first member of this class of alkaloids and was obtained from the stem bark of G. pentaphylla (95,96). In 1991, glycozoline (86) was also isolated by McChesney and El-Feraly from the roots of C. lansium (23). In Taiwan, the roots of this ornamental tree are used in traditional medicine for the treatment of bronchitis and malaria (23). In 1999, Chakravarty et al. isolated glycozoline (86) from the roots of G. arborea (62). 

The UV spectrum (/Imax 246, 251, 257, 307, and 341 nm) of cyclomahanimbine (151) indicates the presence of a carbazole framework with an ether oxygen at C-2. This assignment was supported by the IR spectrum [v ax 1602, 1615 (aromatic system), and 3425 (NH) cm ]. On hydrogenation, cyclomahanimbine yielded the corresponding dihydro derivative, which did not show any shift of the absorption... 

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