9-Formyl-3-methylcarbazole

In 1997, Chakrabarty et al. reported the isolation of 9-carbethoxy-3-methylcarba-zole (5) and 9-formyl-3-methylcarbazole (6) from the roots of M. koenigii (17). These metabolites are the first 9-formyl and 9-carbethoxy carbazole derivatives obtained from plant sources. 9-Formyl-3-methylcarbazole (6) showed weak cytotoxicity against both mouse melanoma B16 and adriamycin-resistant P388 mouse leukemia cell lines. The structural assignment of these two alkaloids was based on the IR- and H-NMR spectra which were lacking any signal of an NH group. Additional structural support for 9-carbethoxy-3-methylcarbazole (5) was provided by the similarity of the UV absorption spectrum with that of a synthetic sample, obtained by reaction of 3-methylcarbazole with ethyl chloroformate in the presence of base. Further structural support for 9-formyl-3-methylcarbazole (6) was derived from a comparison of the UV spectrum and the IR carbonyl absorption (1696 cm ) with those of an authentic sample of 9-formyl-3-methylcarbazole (1700 cm ), prepared by the treatment of 3-methylcarbazole (2) with 98% formic acid (17) (Scheme 2.3). 

Formyl-3-methoxy-6-methylcarbazole (8-Formyl-6-methoxy-3-methylcarbazole) R H R =Me R = CHO... 

A second method involves the well-known Wittig reaction, one example of which is the preparation6 of jV-methyl-3-styrylcarbazole (3) from the corresponding 3-formyl-JV-methylcarbazole. 

Non-tryptamines.—The number of carbazole derivatives isolated from the Rutaceae is now fourteen. Besides the tricyclic compounds murrayanine " (3-formyl-l-methoxycarbazole), glycozoline " (3-methoxy-6-methylcarbazole), glycozolidine " (2,4-dimethoxy-6-methylcarbazole), and (from Clausena hepta-phylla) heptaphylline (1), tetra- and penta-cyclic carbazoles have been obtained from Murraya koenigU3 ... 

Heptaphylline (1) has been synthesised by sequential C(3)-formylation and C(l)-isopentenylation of 2-hydroxycarbazole. l-Formyl-2-hydroxy-3-methyl-carbazole reacts with the Wittig reagent from 2-methylprop-l-en-3-yltriphenyl-phosphonium chloride-sodium hydroxide to generate girinimbine (2a) 2-hydroxy-3-methylcarbazole reacts with citral to give ( )-mahanimbine (3a). 

Of the two structures which had been indicated for this compound, that represented by 99 was considered the more probable. It has been synthesized. l-Formyl-2-hydroxy-3-methylcarbazole (98) was prepared in two stages from 2-methoxy-3-methylcarbazole. The hydroxyalde-hyde was converted into the pyran derivative 99 by a procedure already recorded, and it proved to be identical with girinimbine. 

Formyl-1-methoxycarbazole (murrayanine) and 3-methylcarbazole (for the first time from natural sources) have been isolated from Clausena heptaphylla Heptazolidine/ a new alkaloid from the same source, has been given the structure (44). Its dihydro-derivative has a u.v. absorption said to be similar to that of 2,3-dimethoxycarbazole. 

Vilsmeier-Haack formylation, followed by oxidation with acidic H2O2 was used to introduce a hydroxy group at C3 in A-methylcarbazole <89T1759>. A TMS group was used for the introduction of a C3 hydroxy group in a carbazole in the course of synthesis of carazostatin by a sequence of mercuri-desilation, hydroboration and oxidation (Equation (104)) <90SL52i>. 

Preparations from the stem bark of the Indian curry-leaf tree, Murraya koenigii Spreng. (Rutaceae) are used externally to cure skin eruptions. Extraction of the stem bark yielded three compounds, two of which appear to be carbazole derivatives, while the third is as yet of unknown character. Murraj anine, C14H11NO2 (mp 168°) was shown by examination of its spectra and reactions, and by conversion into 3-methylcarbazole and 1-methoxycarbazole, to be either 6-formyl-l-methoxycarbazole or 3-formyl-1-methoxycarbazole (IV), probably the latter (19). This conclusion has now" been confirmed by an unambiguous synthesis (30). 4-Bromo-o-anisidine was converted bj diazotization followed by reduction with stannous chloride into 4-bromo-2-methoxy-])henylh drazine (V). Condensation of V w ith cyclohexanone and cj cli-... 

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