Novel Route to 2,3-Substituted Benzo[b]thiophenes via Intramolecular Radical Cyclization.

A novel route to 2,3-substituted benzo[b]thiophenes by intramolecular radical cyclization of polarized ketene dithioacetals derived from o-bromoarylacetonitriles or the corresponding 3-(methylthio)-3-alkyl/aryl/heteroaryl analogues has been reported.

Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-alpha and IL-6 inhibitors.

In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-alpha and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60-65% inhibition at 10 microM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC(50)'s of 0.2, 0.3 and 0.16 microM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 microM.

Dipolar cycloaddition of ethyl isocyanoacetate to 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines: highly regio- and chemoselective synthesis of substituted imidazo[1,5-a]quinoxaline-3-carboxylates.

An efficient route for regio- and chemoselective synthesis of substituted 3-(carboethoxy)imidazo[1,5-a]quinoxalines and novel diimidazo[1,5-a:5',1'-c]quinoxalines via base-induced cycloaddition of ethyl isocyanoacetate to unsymmetrically substituted 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines has been reported.

Domino carbocationic rearrangement of alpha-[bis(methylthio)methylene]alkyl-2-(3/2-indolyl) cyclopropyl ketones.

Domino carbocationic rearrangement of a number of substituted 3- and 2-indolylcyclopropyl ketones with an alpha-bis(methylthio)methylene group in the presence of various protic/Lewis acids yields a variety of products, mainly the pentaleno fused indoles and the carbazole derivatives.

An efficient highly regioselective synthesis of 2,3,4-trisubstituted pyrroles by cycloaddition of polarized ketene S,S- and N,S-acetals with activated methylene isocyanides.

An efficient route for regioselective synthesis of 2,3,4- substituted pyrroles allowing precise control over the introduction of a number of substituents and functionalities (tosyl, carbalkoxy, aryl, cyano, nitro, acetyl, benzoyl, cyclic amines, etc.) at the three positions of the pyrrole ring has been developed via 1,3-dipolar cycloaddition of readily accessible polarized ketene S,S- and N,S-acetals with carbanions derived from activated methylene isocyanides.

Palladium-catalyzed intramolecular N-arylation of heteroarenes: a novel and efficient route to benzimidazo[1,2-a]quinolines.

An efficient new route for the synthesis of benzimidazo[1,2-a]quinolines has been developed via the palladium-catalyzed intramolecular Buchwald-Harwtig aryl amination of newly synthesized 2-(2'-bromoanilino)quinolines.

Regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles.

[reaction: see text] Highly efficient and regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles has been reported via cyclocondensation of arylhydrazines with either alpha-oxoketene dithioacetals or beta-oxodithioesters.

Highly regioselective synthesis of 1-aryl-3 (or 5)-alkyl/aryl-5 (or 3)-(N-cycloamino)pyrazoles.

[Reaction: see text]. An efficient highly regioselective protocol for the synthesis of isomeric 1,3-diaryl (or 1-aryl-3-alkyl) and 1,5-diaryl (or 1-aryl-5-alkyl)-5 (or 3)-(N-cycloamino)pyrazoles has been reported by cyclocondensation of common alpha-oxoketene N,S-acetal precursors with arylhydrazines by variation of reaction conditions.

Heteroannulation of nitroketene N,S-arylaminoacetals with POCl3: a novel highly regioselective synthesis of unsymmetrical 2,3-substituted quinoxalines.

[reaction: see text]. A novel regioselective route for the synthesis of substituted and fused 3-chloro-2-(methylthio)quinoxalines through POCl3-mediated heteroannulation of a range of alpha-nitroketene N,S-anilinoacetals has been reported.

A concise formal synthesis of alkaloid cryptotackiene and substituted 6H-indolo[2,3-b]quinolines.

A five-step formal synthesis of alkaloid cryptotackiene and its 2-formyl, 11-methyl/phenyl derivatives involving conjugate addition of enolate anion from cyclohexanone (or 4-methylcyclohexanone) to bis[(methylsulfanyl)methylene]-2-oxindole followed by heterocyclization in the presence of ammonium acetate as the key step has been developed. The 11-methylsulfanyl group in the initial precursor can be either desulfurized (Raney Ni) or replaced by methyl/phenyl groups via nickel-catalyzed cross-coupling reaction with appropriate Grignard reagents.

Reaction of alpha-oxoketene-N,S-arylaminoacetals with Vilsmeier reagents: an efficient route to highly functionalized quinolines and their benzo/hetero-fused analogues.

A simple, highly efficient, and regioselective synthesis of functionalized quinolines through Vilsmeier cyclization of a variety of alpha-oxoketene-N,S-anilinoacetals has been reported. The cyclization is found to be facile with N,S-acetals bearing strongly activating groups on aniline, whereas yields of quinolines are moderate in other cases. The reaction could also be extended for the synthesis of substituted tricyclic benzo[h]quinoline, pyrido[2,3-h]quinoline, 4,7-diphenylphenanthroline, and tetracyclic quino[8,7-h]quinoline by performing a Vilsmeier reaction on N,S-acetals derived from 1-naphthylamine, m-phenylenediamine, o-phenylenediamine, and 1,5-diaminonaphthalene, respectively. A few of the newly synthesized quinolines are subjected to further transformation to afford 2-unsubstituted (Raney-Ni/Ethanol), quinoline-5,8-quinone (NBS/H(2)SO(4)), or 2-alkyl/aryl aminoquinolines through sequential m-CPBA oxidation to the corresponding (2-methylsulfonyl)quinoline followed by replacement with appropriate amines. Similarly, cycloannulation of a few 2-methylthio-3-benzoylquinolines with hydrazine hydrate under microwave irradiation afforded the corresponding substituted and fused pyrazolo[3,4-b]quinolines in excellent yields, whereas TBTH/AIBN-mediated cyclization of the corresponding 3-(2-bromobenzoyl)-2-methylthioquinolines yielded the corresponding benzothiopyrano-fused quinolines through radical translocation.

Heteroaromatic annulation of 2-methyl/2-cyanomethylbenzimidazole dianions with alpha-oxoketene dithioacetals: a highly regioselective synthetic protocol for 1,2- and 2,3-substituted/annulated pyrido[1,2-a]benzimidazoles.

A highly efficient and regioselective annulation protocol for a series of linearly 2,3- and angularly 1,2-substituted and annulated pyrido[1,2-a]benzimidazoles involving [3 + 3] cyclocondensation of the dianions generated from 2-methyl (2A) and 2-cyanomethyl (3A) benzimidazoles with a variety of alpha-oxoketene dithioacetals has been reported. Thus the dianion 2A derived from 2-methylbenzimidazole has been shown to undergo regioselective 1,2-addition with various alpha-oxoketene dithioacetals derived from acyclic (4a-d) and cyclic ketones (13a,b, 20, 29 and 32) to afford various carbinol acetals which on intramolecular cyclocondensation in the presence of phosphoric acid furnish the corresponding 1-methylthio-2,3-substituted (5a-c) and 2,3-fused linear polycyclic (14a,b,21, 30, and 33) pyrido[1,2-a]benzimidazoles in high yields. Similarly the dianion 3A from 2-cyanomethylbenzimidazole undergoes one-pot conjugate addition-elimination and cyclocondensation with these alpha-oxoketene dithioacetals to give 4-cyano-3-(methylthio)-1(or 1,2-)-substituted (6a-d) and the corresponding angularly 1,2-fused (16a,b, 23, 31, and 34) polycylic analogues of pyrido[1,2-a]benzimidazoles in excellent yields.

Domino carbocationic rearrangement of aryl-2-(1-N-methyl/benzyl-3-indolyl)cyclopropyl ketones: a serendipitous route to 1H-cyclopenta[c]carbazole framework.

Aryl-2-(N-methyl/benzyl-3-indolyl)cyclopropyl ketones 2a-m are shown to undergo a novel unexpected domino carbocationic rearrangement in the presence of SnCl(4)/CH(3)NO(2) yielding 2-aroyl-3-aryl-1H-cyclopenta[c]carbazoles 3a-m in good yields. The possible mechanistic pathway for this interesting transformation involves a series of cascade events, (a) electrophilic ring opening of cyclopropyl ketone, (b) intermolecular enol capture of the resulting zwitterionic intermediate, (c) electrophilic dimerization of indole moieties to give tetrahydrocarbazole intermediate and its subsequent aromatization by elimination of an indole moiety and dehydrogenation, and (d) intramolecular aldol condensation of the side chain to give a cyclopentene ring. The overall transformation involves formation of three carbon-carbon bonds along with a fused benzene and a substituted cyclopentene ring in one-pot operation from simple indole precursors.

An expedient route to 2,3-substituted and fused benzo[a]quinolizine-4-thione framework via ring annulation with beta-oxodithioesters.

[figure: see text] An efficient highly convergent route to hitherto unreported 2,3-substituted and annulated benzo[a]quinolizine-4-thiones 3 has been developed. The methodology involves ring annulation of 3,4-dihydro-6,7-dimethoxy-1-methylisoquinoline 1 with a variety of readily accessible acyclic and cyclic beta-oxodithioesters 2 in the presence of triethylamine in refluxing benzene. These benzo[a]quinolizine-4-thiones can be readily converted to the corresponding benzo[a]quinolizine-4-ones 5 via dethiomethylative hydrolysis of the respective benzo[a]quinolizinium salts 4 obtained by alkylation of 3 with methyl iodide.

A new route to spiropyrrolidinyl-oxindole alkaloids via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]-2-oxindoles.

A new approach for the synthesis of spiropyrrolidinyloxindole alkaloids, i.e. coerulescine (4) and horsfiline (5) has been developed via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]oxindoles 2 to the respective spiropyrroline-2-oxindole derivatives 3 and their subsequent one-pot reductive dethiomethylation-N-methylation. [reaction: see text]

In vitro screening of potential anti-cancer chemicals: effect of purine pyrimidine analogues on seed germination.

Germinating Cicer arietinum seeds were used to simulate embryonic tissue for evaluating toxicity of purine and pyrimidine analogues. 6-Mercaptopurine stimulated germination, whereas 8-azaadenine, 8-azaguanine, 2,6-diaminopurine, 6-amino, 2-hydroxypurine and 5-fluorouracil inhibited germination. 6-Methyluracil, 5-aminouracil and methylxanthines, viz. caffeine, theophylline, theobromine and uric acid exhibited little inhibitory effects. RNA synthesis ensued immediately after water imbibition and reached maximum at 12 h of germination. 2,6-Diaminopurine, 8-azaadenine, 8-azaguanine and 5-fluorouracil inhibited RNA synthesis. Cyclic-AMP, adenosine, indole-3-acetic acid (IAA) and folic acid partially reversed the inhibitory effects produced by purine pyrimidine analogues. Several hitherto untested pyrimidine analogues inhibited germination as well as RNA synthesis. Inhibition of Escherichia coli dihydrofolate reductase was used for purposes of comparison.