9-Methyl-3-hydroxycarbazole

In 1993, Kusano et al. isolated 2-hydroxy-7-methyl-9H-carbazole (243) from the aerial parts of Cimicifuga simplex Wormsk. ex DC. (224). Six years later, Wu et al. reported the isolation of clausine V (244) from the root bark of C. excavata (43) (Scheme 2.60). The UV spectrum (/max 236, 261, and 305 nm) of 2-hydroxy-7-methyl-9H-carbazole (243) indicated a 2-hydroxycarbazole. This assignment was supported by the IR spectrum [Vmax 1611 (aromatic system), 2700-3000 (OH), and 3400 (NH) cm ]. The presence of a hydroxy function was confirmed by transformation into the corresponding 0-acetate and comparison with 2-hydroxy-7-methyl-9H-carbazole. 

The thermal cyclization of 3-(l,3-butadienyl)indoles 692 in refluxing cis-decalin afforded the carbazoles 698. Selective hydrolysis of the 3-carbonate ester, methylation of the corresponding 3-hydroxycarbazoles 699 with methyl iodide in the presence of... 

The total synthesis of carbazomycin D (263) was completed using the quinone imine cyclization route as described for the total synthesis of carbazomycin A (261) (see Scheme 5.86). Electrophilic substitution of the arylamine 780a by reaction with the complex salt 779 provided the iron complex 800. Using different grades of manganese dioxide, the oxidative cyclization of complex 800 was achieved in a two-step sequence to afford the tricarbonyliron complexes 801 (38%) and 802 (4%). By a subsequent proton-catalyzed isomerization, the 8-methoxy isomer 802 could be quantitatively transformed to the 6-methoxy isomer 801 due to the regio-directing effect of the 2-methoxy substituent of the intermediate cyclohexadienyl cation. Demetalation of complex 801 with trimethylamine N-oxide, followed by O-methylation of the intermediate 3-hydroxycarbazole derivative, provided carbazomycin D (263) (five steps and 23% overall yield based on 779) (611) (Scheme 5.91). 

In addition to the aforementioned syntheses of various carbazole-l,4-quinone alkaloids, many formal syntheses for this class of carbazole alkaloids were also reported. These syntheses involve the oxidation of the appropriate 1- or 4-oxygenated-3-methylcarbazoles using Fremy s salt (potassium nitrosodisulfonate), or PCC (pyridinium chlorochromate), or Phl(OCCXI F3)2 [bis(trifluoroacetoxy)iodo]-benzene. Our iron-mediated formal synthesis of murrayaquinone A (107) was achieved starting from murrayafoline A (7) (see Scheme 5.34). Cleavage of the methyl ether in murrayafoline A (7) and subsequent oxidation of the resulting intermediate hydroxycarbazole with Fremy s salt provided murrayaquinone A (107) (574,632) (Scheme 5.113). 

The relay compound 1025 required for the synthesis of all of these 7-oxygenated carbazole alkaloids was obtained starting from commercially available 4-bromo-toluene (1023) and m-anisidine (840) in two steps and 72% overall yield. Buchwald-Hartwig amination of 4-bromotoluene (1023) with m-anisidine (840) furnished quantitatively the corresponding diarylamine 1024. Oxidative cyclization of 1024 using catalytic amounts of palladium(ll) acetate afforded 3-methyl-7-methoxycarbazole (1025). Oxidation of 1025 with DDQ led to clauszoline-K (98), which, on cleavage of the methyl ether using boron tribromide, afforded 3-formyl-7-hydroxycarbazole (99) (546) (Scheme 5.149). 

An alternative procedure, which was devised for the synthesis of heteroannulated chromenes, involves the reaction of the titanium salt of the phenol with an a, 3-unsaturated carbonyl compound. " This is illustrated for the reaction of iV-methyl-3-hydroxycarbazole (1.26) with P-phenylcinnamaldehyde, which produces the carbazolopyran (1.27) in 35% yield. ... 

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyi-l-methylpyrrole and with 3-formylindole produces (443 Hetero= l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

At 140° in methanol, a much more extensive decomposition of akuammicine occurs, and the products isolated are 3-ethylpyridine and 2-hydroxycarbazole (XXXV). The formation of 3-ethylpyridine is presumably the result of a normal Hofmann degradation of the pyri-dinium ester corresponding to XXXIII the other product should consequently have been methyl 3-vinyl-2-indolylacetate (XXXIV), but this was not obtained. It was accordingly suggested that the 2-hydroxycarbazole obtained was formed from XXXIV by intramolecular nucleophilic attack of the vinylogous enamine methylene group on the carbomethoxy group (arrows in XXXIV), followed by elimination of methanol and aromatization (39). 

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). 

Five-membered heterocyclic amines have been attracting attention for a long time. Their antioxidant effect was confirmed in model experiments. Derivatives of indole and carbazole are HS for PVC and copolymers of vinyl chloride [92], Some indoles are medical or biological AO protecting against chemical carcinogenesis or chemically induced hepatoxicity [93]. 6-Hydroxycarbazole suppresses oxidation of methyl linoleate, its sacrificial transformation yields a QI. 2,2-Disubstituted l,2-dihydro-3-oxo(or phenylimino)-3//-indoles (15a, b, R = Me, Et) have a potential importance as HS for PO [36]. 

Hydroxycarbazole containing a methyl group at different positions of the carbazole nucleus produces different bases (91) when reacted with citral (148) in a mixture of acetic acid and butanol at 110°. A mixture of... 

---