Indolo quinolines, synthesis

The Friedlander quinoline synthesis was applied in a one-step synthesis of 67/-indolo[3,2-fe]naphthyridines (azaellipticines) by Queguiner s team by condensing A -acetylindoxyl with aminofomyl pyridines (Scheme 15,... 

The synthesis and antitumour activity of glycoylamino-indolo-quinolines is mentioned in Chapter 10. Glycosyloxyphenyl derivatives of mitomycin A have been prepared, but they offered no... 

The Graebe-Ullman carbazole synthesis has been enmloyed in the preparation of substituted carbolines, as well as indolo[2,3-i] quinolines, which are often difficult to synthesize via other approaches, for example, the Fischer indole process. 

The yellow colored, sparcely soluble 5-ethyl-2-methyl-l l/f-pyrido[3,4-u] carbazolium 347 isolated from Aspidosperma gilbertii exists as a hydroxide after filtration of the corresponding iodide over basic aluminum oxide. A short synthesis was described (80CB3245). The Pyrido[3,4-a]carbazole ring system is present in the alkaloid AG-1, whereas Cryptolepine (348) possesses the indolo[3,2-b]quinoline moiety (65MI1). 

Guyen B et al. (2004) Synthesis and evaluation of analogues of 10H-indolo[3,2-b] quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase. Org Biomol Chem 2(7) 981-988... 

Synthesis of this compound began with the condensation of O, N-acetyl-indoxyl 174 with 5-bromoisatin 175 to give indolo [ 3,2-fo ] quinoline 176 after stirring at room temperature for 10 days (Fig. 49) [104]. This product was then decarboxylated by heating at reflux for 6 h in diphenyl ether. Yields were... 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

Interaction of substituted dienediamines with ethylenediamine yields im-idazo[3,2-n]pyridine derivatives (95JHC477). 3-Arylaminoindoles, with distinct enamine properties, are the starting materials for the synthesis of indolo[3,2-b]quinoline derivatives [96KFZ(7)42]. a-Carboline derivatives can be obtained from enamine-based 3-dimethylamino-2-indolinones [96KFZ(9)35, 96KFZ(10)32], The synthesis and transformation of enamines based on the pyrido[l,2-n]pyrazine ring system into imidazo[l,2-n]pyridine and imidazo[l,2-a]pyrimidine derivatives have been reported... 

Caprio et al. (in 2000) reported the synthesis and inhibitory profile of a novel quinoline derivative against human telomerase [27]. The molecule bis-dimethylaminoethyl is a derivative of quindoline (10H-indolo[ 3,2-fo] quinoline) (for structure see Fig. 3), an alkaloid from the West African shrub Cryp-tolepis sanguinolenta, as reported by the authors [27]. The compound exhibits moderate cytotoxicity and inhibitory activity against telomerase. Utilizing molecular modelling technology, the authors hypothesized that the inhibitory... 

The analogous photocyclisation of enamides is well known and is of particular value in synthesis. Photocyclisation of the enamides (29) to the furopyridones (30), for example, has been used in the preparation of key intermediates for alkaloid synthesis. Similar approaches have been employed in the synthesis of corynanthe alkaloids ° and in the preparation of trans-hexahydro-indolo[43-ab]phenanthridines as selective dopamine agonists. The benzoylmethylenebenzothiazepines (31) can be converted in the same way into the B-homo-5-thiaprotoberberines (32). Enamide photocyclisation has also been employed in the syntheses of halo-benzofuro[2,3-c]quinolines,benzo[h][l]- and benzo[/j[1]-benzo-... 

Formation of indole derivative by the reaction of 2-ethynylaniline, aryl halide and CO is known [53]. Cacchi extended the reaction to the synthesis of indolo[3.2-c]quinoline. Reaction of 2-(2 -aminophenylethynyl)trifluoroacetanilide 122, 4-iodoanisole and CO occurred as shown by 123 to provide 124 and then the 3-aroylindole 125. Treatment of 125 with a base gave the indoloquinoline 126 in 70% overall yield [54]. 

Myriad examples are known of oxindoles reacting to form indoles without prior carbonyl activation. Given (he vast scope of this subject, only a few early examples will be cited in addition to recent studies. Several groups have annulated oxindoles to access fused-indole heterocycles. Ila, Junjappa, and coworkers prepared pyrido[2,3-( ]indoles [61, 62] and 67/-indolo[2,3-fc]quinolines [63] using this approach (Scheme 9, equation 1). Adib and colleagues reported a simple synthesis of 9/7-pyrimido[4,5-Z ]indoles from oxindoles (eqnation 2) [64], and Bazgir and coworkers described a four-component one-pot a-carboUne synthesis... 

The methodology has also been applied to the synthesis of functionalized indolo[3,2-c] quinolines by employing o-Co -aminophenylethynyOtrifluoroacetanilide and aryl iodides as substrates (Scheme 20). The desired indolo[3,2-c]quinolines can be prepared by a stepwise procedure involving the isolation of an acylindole intermediate or by a one-pot process, which usually gives higher yields. 

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