Formylcarbazole

O-Demethylmurrayanine (217) C13H9NO2 (M 211), m.p. 237-39° was isolated from stem and root bark of Clausena anisata (55). The uv spectrum 226, 244, 255, 278, 291, 336, 346 nm with log e 4.40,4.51, 4.39,4.59,4.45,4.22,4.22) showed it to be a 3-formyl carbazole derivative. This and colour reactions showed it to be a phenolic carbazole. The H-NMR spectrum indicated the presence of deshielded metacoupled H-4 and H-2 protons, the four protons of the ring A and the proton of the CHO group (89.89). Hence the alkaloid was formulated as l-hydroxy-3-formyl-carbazole. The C-NMR spectrum also support the structure. 

3-Formylcarbazole (218) C13H9NO2 (M 195.0683) was obtained as a colourless oil from Murraya euchrestifolia (59). The uv spectrum was characteristic for a 3-formylcarbazole which was also supported by the ir and H-NMR spectra. 

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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). 

Methoxymurrayanine (3) (3-formyl-l,6-dimethoxycarbazole) (15) was isolated from the roots of C. lansium (23). The roots of C. lansium were used to treat bronchitis and malaria. The UV (/Imax 227, 239, 251, 294, 335, and 349 nm) and IR spectra showed the presence of a 3-formylcarbazole framework. The H-NMR data were similar to murrayanine (9), with an additional methoxy group for one of the aromatic hydrogens at the C-ring of the carbazole. Since the signal for H-5 (5 7.90) is not ortho-coupled, an additional methoxy could be located at C-6. This structural conclusion was also supported by the C-NMR spectrum. 

The UV spectrum (/Imax 223, 242, 255, 278, 296, 341, and 353 nm) of clausine I (30) resembled that of O-demethylmurrayanine (24), which suggests a l-hydroxy-3-formylcarbazole framework. The presence of a hydroxy group and a conjugated aldehyde group was further confirmed in the IR spectrum by strong absorptions at 3400 and 1640 cm , respectively. The H-NMR spectrum was similar to that of... 

In 1992, Furukawa et al. reported the isolation of 3-formyl-7-hydroxycarbazole (99) from the root bark of M. euchrestifolia (104). The UV spectrum [2max 233,245 (sh), 273, 288, and 326 nm] and the IR spectrum (v ax 1673 and 3336 cm ) of 3-formyl-7-hydroxycarbazole were very similar to those of clauszoline-K (98), indicating a 3-formylcarbazole framework. The H-NMR spectrum confirmed the structural similarity to clauszoline-K, and showed the presence of a hydroxy group instead of the methoxy group. All of the spectroscopic data supported the structure of 3-formyl-7-hydroxycarbazole (99) (Scheme 2.19). 

In 1990, Lange et al. isolated 7-methoxymurrayacine (125) from the roots of M. siamensis (57). The UV and IR spectra of 7-methoxymurrayacine (125) were very similar to those of murrayacine (124) indicating a 3-formylcarbazole. The H-NMR spectrum of 7-methoxymurrayacine also resembled that of murrayacine. However, the C-ring substitution pattern was similar to that of murrayamine-A (120) (see Scheme 2.22), indicating the presence of a substituent at C-7. This regiochemical assignment was supported by the H-NMR spectrum which showed an ortho-coupled (7=8.4 Hz) H-5 at 7.84, an ortho- and mete-coupled (/=8.4, 2.2 Hz) H-6 at 5 6.86, and a mete-coupled (/=2.2 Hz) H-8 at S 6.90. These spectroscopic data led to structure 125 for 7-methoxymurrayacine. 

In 1996, Wu et al. reported the isolation of murrayamine-M (162), a formyl analog of bicyclomahanimbicine (161) from the leaves of M. euchrestifolia collected in November in Taiwan. The UV spectrum Umax 243, 254 (sh), 292, and 325 nm] of murrayamine-M (162) indicated a 3-formylcarbazole. This assignment was supported by the IR spectrum [Vmax 1605 (aromatic system), 1675 (CHO), and 3300 (NH) cm J. The H-NMR spectrum resembled that of bicyclomahanimbicine (161), but exhibited a formyl group ( 10.08) at C-3 instead of the aromatic methyl group. The deshielded mete-coupled (/=1.7Hz) H-4 at 6 8.48 confirmed the position of the formyl group at C-3. Based on the spectral data, structure 162 was assigned to murrayamine-M (Scheme 2.32). The absolute configuration of 162 is not known (130). 

In 1996, Ito et al. reported the isolation of clauszoline-A (167) and clauszoline-B (168) from the acetone extract of the stem bark of C. excavata collected in Singapore (74). These alkaloids represented the first, naturally occurring 2,8-dioxygenated-3-formylcarbazole alkaloids with a dimethylpyran ring fused to C-7 and C-8 of the carbazole nucleus. The extracts of the leaves and bark of this tree have been used in traditional medicine for the treatment of snakebites and abdominal pain (74). One year later, the same group isolated another pyrano[2,3-fl]carbazole alkaloid, clauszoline-H (169), from the roots of the same natural source in Japan (47) (Scheme 2.34). 

In 2003, Sunthitikawinsakul et al. described the anti-mycobacterial activity of various 3-methylcarbazole derivatives, including 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), clausine K (clauszoline-J) (51) (see Scheme 2.11), and 7-methoxymukonal (68) (see Scheme 2.14) against Mycobacterium tuberculosis H37Ra. Except for clausine K (clauszoline-J) (51), all of these alkaloids also showed anti-fungal activity against Candida albicans (442). In 2005, Eranzblau et al. reported the in vitro anti-TB activity of various carbazole derivatives such as 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), lansine... 

In 2000, Boyd et al. reported for the first time an anti-HIV active carbazole alkaloid, siamenol (89) (see Scheme 2.17). This prenylated carbazole alkaloid inhibited HIV-1 induced cytopathic inhibitor activity in an XTT-tetrazolium assay with EC50 2.6 pg/mL (85,449). Recently, Kongkathip et al. reported anti-HIV-1 activity for O-methylmukonal (glycosinine) (38) (see Scheme 2.9), 7-methoxy-O-methylmu-konal (2,7-dimethoxy-3-formylcarbazole) (48) (see Scheme 2.10), and clausine K (clausazoline-J) (51). These studies showed strong anti-HIV-1 activity for... 

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