Synthesis of pyrano[3,2-]chromene-2,5-diones from 4-hydroxycoumarins and aminocrotonates under solvent-free conditions.

A new one-pot approach was developed for the construction of pyrano[3,2-]chromene-2,5-diones by reacting 4-hydroxycoumarins with ethyl 3-oxo-3-phenylpropanoates in the presence of ammonium salts or aminocrotonates under solvent-free conditions. The title compounds were formed by intramolecular cyclization through new C-C and C-O bonds. Structure assignment of compound 3e was confirmed by single crystal X-ray analysis.

-TSA catalyzed 6-/ cyclization of 5-aminopyrazoles and 3°/2°-propargylic alcohols: access to pyrazolo[1,5-]dihydropyrimidines and pyrazolo[3,4-]pyridines.

A facile, straightforward synthesis of fused pyrazolo[1,5-]dihydropyrimidines and pyrazolo[3,4-]pyridines is accomplished by using 5-aminopyrazoles, 3°/2°-propargylic alcohols and ynones in the presence of -TSA. The reaction proceeds through allenylation (-alkylation)/propargylation (-alkylation) of 5-aminopyrazoles, followed by intramolecular 6-/ cyclization leading to the title products with the formation of new C-N and C-C bonds. Operationally simple reaction conditions, inexpensive reagents, better yields, and gram-scale synthesis are the advantages of this protocol.

One-pot domino synthesis of five- and six-membered fused dihydropyridines promoted by PPh-NBS in aqueous medium.

A facile one-pot synthesis of five- and six-membered fused dihydropyridines such as chromenodihydropyridines, pyrazolodihydropyridines and isoxazolopyridines was accomplished for the first time by employing PPh-NBS a formal [3 + 2 + 1] cycloaddition of 1,3-bisnucleophiles (, 2-aminochromone, 4-aminochromone, 5-aminopyrazole and 5-aminoisoxazole), β-enaminones and aldehydes in aqueous medium. The present approach involves a Michael type addition followed by intramolecular cyclization leading to the formation of two new C-C bonds and one C-N bond. High compatibility and excellent yields are the advantages of this protocol.

NaS-promoted reduction of azides in water: synthesis of pyrazolopyridines in one pot and evaluation of antimicrobial activity.

Reduction of various azides using Na2S has been accomplished in water, and, in situ, the resulting amines on reaction with various ketones lead to pyrazolo[3,4-b]pyridines in one pot. Thus, a number of new trifluoromethyl-substituted pyrazolo[3,4-b]pyridine compounds have been prepared and screened for antimicrobial activity against different Gram-positive and Gram-negative strains. A good number of compounds, 4a, 4b, 4d, 4f, 4i, 4k, 4l, 4m, 4r and 4s, were found to possess promising activity.

A simple, one pot synthesis of furo[3,2-c]chromenes and evaluation of antimicrobial activity.

Synthesis of a number of 2-cyano-4-oxo-3-phenyl-3,4-dihydro-2H-furo[3,2-c]chromene-2-carboxylate compounds (5) have been accomplished by a simple, multicomponent one pot reaction and evaluated for in vitro antimicrobial activity against different Gram-positive and Gram-negative bacterial strains. The outcome of the screening study showed that compound 5c exhibited promising activity against Micrococcus luteus MTCC 2470 and Klebsiella planticola MTCC 530. Whereas, compound 5g exhibited excellent activity against Bacillus subtilis MTCC 121, Micrococcus luteus MTCC 2470, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739 and displayed a moderate activity against Staphylococcus aureus MTCC 96 and Candida albicans MTCC 3017 when compared with Ciprofloxacin (standard control).

One pot oxidative N-S bond formation to access 2-sulfenylimine chromenes.

The synthesis of 2-sulfenylimine chromene compounds (8) is accomplished by reacting benzaldehyde (1), malanonitrile (2) and dimedone (3) followed by sequential addition of N-chlorosuccinimide and thiophenols to the in situ formed 2-amino-4(H) chromenes (4) in a one pot, catalyst free, five component reaction in toluene medium. When aniline was employed as the nucleophile in place of thiophenol, the formation of hexahydrobenzofuran-2-N-phenyl carboxamide derivatives (5) was observed. Excellent yields, simple reaction conditions and high compatibility are the advantages of this protocol.

Synthesis and evaluation of novel fluorinated pyrazolo-1,2,3-triazole hybrids as antimycobacterial agents.

A library of novel 3-trifluoromethyl pyrazolo-1,2,3-triazole hybrids (5-7) were accomplished starting from 5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-amine (1) via key intermediate 2-azido-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acetamide (3) through click chemistry approach. Thus obtained compounds in 5-7 series were evaluated for in vitro antimycobacterial activity against Mycobacterium smegmatis (MC(2) 155) and also verified the cytotoxicity. These studies engendered promising lead compounds 5q, 7b and 7c with MIC (μg/mL) values 15.

One-pot catalyst free synthesis of novel kojic acid tagged 2-aryl/alkyl substituted-4H-chromenes and evaluation of their antimicrobial and anti-biofilm activities.

A number of 3-hydroxy-6-(hydroxymethyl)-2-(2-phenyl-4H-chromen-4-yl)-4H-pyran-4-ones (3) have been synthesized in a one pot catalyst free reaction of 2-hydroxy chalcone (1) with kojic acid (2) in toluene at reflux temperature and evaluated for antimicrobial and anti-biofilm activities. Compounds 3a, 3e, 3f, 3l showed potent antimicrobial activity against Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, whereas 3b and 3k exhibited excellent activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, while 3g showed promising activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739. On the other hand, compounds 3a, 3b and 3l showed very good anti-biofilm activity and 3g showed moderate activity against Bacillus subtilis MTCC 121.

Regioselective synthesis of 3-benzyl substituted pyrimidino chromen-2-ones and evaluation of anti-microbial and anti-biofilm activities.

Regioselective synthesis of a number of highly functionalized 3-benzylpyrimidino chromen-2-ones (4) were accomplished in a one pot three component reaction in acetic acid and determined their anti-microbial and anti-biofilm activities. Compounds 4o and 4p showed an excellent anti-microbial activity against Micrococcus luteus MTCC 2470 at a par with standard control (Ciprofloxacin) and exhibited best activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121. Further, compounds 4h, 4i, 4m, 4n and 4q showed promising activity against Micrococcus luteus MTCC 2470, Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121.

Synthesis and cytotoxicity evaluation of highly functionalized pyranochromenes and pyranopyrans.

A series of fluorinated tetrahydropyrano[3,2-c]chromenes and dihydropyrano[3,2-b]pyran derivatives have been synthesized and their in vitro cytotoxic activities have been determined in cervical cancer cell line (HeLa), human breast adenocarcinoma cell line (MDA-MB-231 and MCF-7) and human alveolar adenocarcinoma cell line (A549). Compounds 4g, 4k, 4p showed a very potent activity against MDA-MB-231, and 4c, 4p showed promising activity against MCF-7, while compounds 4c, 4g, 4p showed moderate activity against HeLa.

Structure-activity relationship study of novel anticancer aspirin-based compounds.

We performed a structure-activity relationship (SAR) study of a novel aspirin (ASA) derivative, which shows strong anticancer activity in vitro and in vivo. A series of ASA-based benzyl esters (ABEs) were synthesized and their inhibitory activity against human colon (HT-29 and SW480) and pancreatic (BxPC-3 and MIA PaCa-2) cancer cell lines was evaluated. The ABEs that we studied largely comprise organic benzyl esters bearing an ASA or acyloxy group (X) at the meta or para position of the benzyl ring and one of four different leaving groups.