Murraya carbazole alkaloids

The dimeric carbazole alkaloids often occur along with the corresponding monomeric carbazoles in terrestrial plants [7,62] (Scheme 7). Clausenamine-A was obtained by Wu from the stem bark of Clausena excavata [63]. Clausen-amine-A and its synthetic analogs, like bis(O-demethylmurrayafoline-A), show cytotoxic activities against diverse human cancer cell lines [64] and exhibit moderate antimalarial activity [65,66]. Furukawa isolated l,r-bis(2-hy-droxy-3-methylcarbazole) and bismurrayaquinone-A, the first dimeric car-bazolequinone alkaloid found in nature, from Murraya koenigii [67]. 

Dineshkumar et al. investigated the antidiabetic efficacy of mahan-imbine (33), a carbazole alkaloid isolated from Murraya koenigii... 

Dineshkumar B, Mitra A, Mahadevappa M. (2010) Antidiabetic and hypolipidemic effects of mahanimbine (carbazole alkaloid) from Murraya koenigii (rutaceae) leaves. Int J Phytomed 2 22-30. 

The isolation of carbazole (1), 3-methylcarbazole (2), and several oxidized derivatives of 3-methylcarbazole from taxonomically related higher plants of the genera Glycosmis, Glausena, and Murraya (family Rutaceae) indicates that the aromatic methyl group of the biogenetic key intermediate 3-methylcarbazole can be eliminated oxidatively (5,6). Most of the carbazole alkaloids isolated from the... 

In 1988, Furukawa et al. isolated murrafoline-E (184) and murrafoline-F (185) from the root bark of M. euchrestifolia. Murrafoline-E was the third example of an N-benzyl-linked bis-carbazole alkaloid from a Murraya plant, while murrafoline-F was the first N-methoxy-bis-carbazole alkaloid (22). 

Wu et al. studied a range of natural carbazole alkaloids isolated from Murraya euchrestifolia for platelet aggregation inhibitory activity, and found that murrayamine A (7-hydroxygirinimbine, mukoenine-C) (120) (see Scheme 2.22) and murrayamine-M... 

The bis-carbazole alkaloids typically contain previously known monomeric carbazoles as structural subunits. To date, bis-carbazole alkaloids have been isolated from plants of two genera of the family Rutaceae, Murraya and Clausena, and are linked either by a methylene unit, a bisbenzylic ether bridge, a bond joining one aromatic portion directly to an annotated dihydropyran unit, or by a biaryl bond. Many reviews have appeared on the monomeric carbazole alkaloids. However, in these articles only a few bis-carbazole alkaloids were listed (3,5-7). For the first time, in 1992, Furukawa et al. compiled all of the bis-carbazole alkaloids that were known to the end of 1992 (158). Taster and Bringmann summarized to the end of 2001, the occurrence, stereochemistry, synthesis, and biological activity of the bis-carbazoles linked through a biaryl bond (159). We compiled to the mid of 2002, the occurrence, stereochemistry, synthesis, and the biological activity of all classes of bis-carbazoles (8). In this section, we cover the total syntheses of the natural bis-carbazole alkaloids reported since 1990. 

Recently, Tripathi et al. reported a new pyrano[3,2-a]carbazole alkaloid, 7-isovaleryl-oxy-8-methoxygirinimbine (1569) from the leaves of Murraya koenigii (896) (Scheme 6.2). 

Rahman, M. M. and Gray, A. I. 2005. A benzoisofuranone derivative and carbazole alkaloids from Murraya koenigii and their antimicrobial activity. Phytochemistry, 66 1601-1606. 

Biologically active carbazole alkaloids from Murraya koenigii. Journal of Agriculture and Food Chemistry, 47 444 47. 

The known alkaloid heptaphylline has been isolated from the roots of Clausena harmandiana Pierre (Rutaceae) along with two new carbazole alkaloids identified as 2-hydroxy-3-formyl-7-methoxycarbazole (58) and 7-methoxyheptaphylline (59). The H- and l3C-NMR spectra have been analyzed and used to position the various functional groups (54,55). Other carbazole alkaloids isolated from the roots of Murraya siamensis Craib are identified as murrayanine, girinimbine, and mukonal, which occur together with heptaphylline and compounds 58 and 59 (56-55). Three new alkaloids have also been isolated from M. siamensis and named 3-formyl-2,7-dimethoxycarbazole (60), 3-formyl-2-methoxylcarbazole (O-methylmukonal) (61), and 7-methoxymurrayacine (62) (59). From the roots of Rauwolfia serpentina, the new alkaloid indobine (63) (60), the benzyl ester, and indobinine (64) (61), the cyclohexyl ester of indolepropionic acid, have been isolated and identified. 

Bhattacharya, L., Roy, S.K. and Chakraborty, D.P. (1982) Structure of the carbazole alkaloid isomurrayazoline from Murraya koenigii [stem bark]. Phytochemistry 21, 2432-2433. 

Bhattacharyya, P., Jash, S.S. and Chowdhury, B.K. (1 986) A biogenetically important carbazole alkaloid from Murraya koenigii Spreng. Chemistry and Industry 7, 246. 

Chowdhury, B.K., Jha, S., Bhattacharyya, P. and Mukherjee, J. (2001) Two new carbazole alkaloids from Murraya koenigii. Indian Journal of Chemistry Section-B 40(6), 490 494. 

Fiebig, M., Pezzuto, J.M., Soejarto, D.D. and Kinghorn, A.D. (1 985) Koenoline, a further cytotoxic carbazole alkaloid from Murraya koenigii. Phytochemistry 24, 3041-3043. 

Ito, C., Thoyama, Y., Omura, M., Kajiura, I. and Furukawa, H. (1 993) Alkaloidal constituents of Murraya koenigii. Isolation and structural elucidation of novel binary carbazolequinones and carbazole alkaloids. Chemical and Pharmaceutical Bulletin 41, 2096-21 00. 

Ito, C., Itoigawa, M., Nakao, K., Murata, T., Tsuboi, M., Kaneda, N. and Furukawa, H. (2006) Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii. Phytomedicine 1 3, 359-365. 

Mukherjee, M., Mukherjee, S., Shaw, A.K. and Ganguly, S.N. (1983) Mukonicine, a carbazole alkaloid from leaves of Murraya koenigii. Phytochemistry 22, 2328-2329. 

Nutan, M.T.H., Hasan, C.M. and Rashid, M.A. (1999) Bismurrayafoline E a new dimeric carbazole alkaloid from Murraya koenigii. Fitoterapia 70(2), 130-133. 

Ramsewak, R.S., Nair, M.G., Strasburg, G.M., DeWitt, D.L. and Nitiss, J.L. (1999) Biologically active carbazole alkaloids from Murraya koenigii. Journal of Agricultural and Food Chemistry 47, 444-447. 

Reisch, J., Adebajo, A.C., Kumar, V. and Aladesanmi, A.J. (1994b) Two carbazole alkaloids from Murraya koenigii. Phytochemistry 36, 1073-1076. 

Sukari, M.A., Ahmad, K., Aimi, N., Kitajima, M., Rahmani, M., Lian, G.E.C. and Ahmad, F.H. (2001) Carbazole alkaloids from stem bark of Murraya koenigii. ACGA Chemical Research Communications 13, 2-8. 

It has also been proposed that the presence of endophytes can alter the usual suite of secondary metabolites of plants. For example, whilst Murraya spp. have been reported to produce indole and carbazole alkaloids, the Brazilian M. paniculata did not [25]. An endophytic Eupenicillium sp. was isolated from surface-sterilized leaf material of the Brazilian M. paniculata and subsequently cultured on white corn. The Eupenicillium sp. produced hydrophobic spiroquinazoline alkaloids that were separated using silica gel column chromatography and preparative gel-filtration... 

Clauszoline-K and dausine C (clauszoline-L) have been isolated from the stem bark of the Chinese medidnal plant Clausena excavata [72], Clausine M and dausine N have been found in the root bark of the same plant [73]. The bioassay-guided fractionation of the organic extract of Murraya siamensis, collected in Thailand, led to the isolation of siamenol, which shows HIV-inhibitory activity [74], A simple route to these 7-oxygenated carbazole alkaloids has been developed, based on a highly efficient palladium-catalyzed approach (Scheme 15.21) [75] (Table 15.4). 

Carbazole alkaloids isolated from Murraya species include murrayamines O 137 and P 138 with a cannabinoid moiety from the root barks of Murraya euchrestifolia <1995TL5385> and the dimeric bismurrayafoline E 139 from Murraya koenigii <1999MI130>. 

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