Clausenae

Coumarins and carbazoles Clausena harmandiana SiOi Hx + AcOEt UV 254 nm Antiplasmoidal activity 86... 

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]. 

In 1988, Furukawa et al. reported the isolation of 3-formylcarbazole (3) from the root bark of M. euchrestifolia (22). Three years later, McChesney and El-Feraly isolated 3-formylcarbazole (3), along with methyl carbazole-3-carboxylate (4), from the roots of Clausena lansium (23). The roots of this ornamental tree are used in traditional medicine in Taiwan to treat bronchitis and malaria (23). In 1992, Bhattacharyya et al. described the isolation and structural elucidation of 3-formylcarbazole (3) from G. pentaphylla (24). 

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. 

Potterat, O., Puder, C., Bolek, W., Wagner, K., Ke, C., Ye, Y. and Gillardon, F. 2005. Clauzine Z, a new carbazole alkaloids from Clausena excavata with inhibitory activity on CDK5. Die Pharmazie, 60 637-639. 

Myricetin 3, 4 -dimethyl ether 3-Rhamnoside Clausena excavata aerial parts Rutaceae 444... 

He, H. et al., Flavonoid glycoside from Clausena excavata, Yunnan Zhiwu Yanjiu, 23, 256, 2001. 

Clausena harmandiana Pierre (root bark) Rutaceae Heptaphylline (54) 2-Hydroxy-3-formyl-7-methoxycarbazole (55) 7-Methoxyheptaphylline (55)... 

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. 

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-... 

Adesina, S.K., Olatunji, O.A., Bergenthal, D. and Reisch, J. (1 988) New biogenetically significant constituents of Clausena anisata and Murraya koenigii. Pharmazie 43, 221-222. 

In conjunction with work in natural products synthesis, the controlled installation of stereocenters alpha to indole C2 remains of significant interest. In their approach to Clausena alkaloids, e.g., (-)-(5R, 6S)-balasubramide, Wang and co-workers employed an intramolecular 8-CMc/o-epoxide-arene cyclization for installation of a C2-C3 8-membered lactam moiety with excellent enantioselectivity <07OL1387>. The Chen group has reported a diastereoselective reaction between 2-lithioindoles and chiral A -terf-but ane sulfinyl... 

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). 

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