Facile Synthesis of Some New Peptidomimetic ß3 -and ß2,3 -Amino Alcohols Possessing Pyridyl Moiety via Reductive Ring Opening of Pyridyl-isoxazolidines.

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-pyridyl)-N-phenylnitrone (2) with variedly substituted dipolarophiles (3, 4) were carried out to obtain substituted pyridyl-isoxazolidines (5-8). Reductive cleavage of pyridyl-isoxazolidines (5-8) with ammonium formate, methanol-THF solvents, at ambient temperature, in the presence of Pd/C provided a facile route for the synthesis of ß3 -and ß2,3 -amino alcohols (9-12), with a substitution pattern having pronounced influence on torsional angles. The obtained compounds (9-12) are valuable scaffolds which can be utilized for peptidomimetics. Thus, the present methodology for reductive opening of isoxazolidine ring avoids the disadvantages of using expensive apparatus and hazards involved in the use of hydrogen gas. The preferential formation of amino-alcohols in case of bicyclic isoxazolidines (8a-c), which precludes any recyclization is rationalized by DFT calculations.

Synthesis and evaluation of some novel chromone based dithiazoles as antimicrobial agents.

Novel substituted 1,2,4-dithiazolylchromones 3a-j were synthesized by the reaction of 3-formylchromones (1a-j) with two equivalents of p-chlorothiobenzamide (2) in dry xylene and characterized spectroscopically (IR, (1)H and (13)C NMR, mass) and elemental analysis. All synthesized compounds were screened for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains and were found to possess good to moderate inhibitory potential against all tested strains. Antimicrobial results reveal that compounds bearing lipophilic electron withdrawing groups such as chloro and bromo displayed significant inhibitory potential against both bacterial and fungal strains. Particularly, compound 3c displayed significant inhibitory against bacterial strains and compound 3h exhibits significant inhibitory potential in comparison to standard drug fluconazole against fungal strain S. cerevisiae.

Synthesis and in vitro cytotoxic activity of chromenopyridones.

Novel substituted chromenopyridones (3a-j and 6a-d) were synthesized and evaluated in vitro for the cytotoxic activity against various human cancer cell lines such as prostate (PC-3), breast (MCF-7), CNS (IMR-32), cervix (Hela), and liver (Hep-G2). preliminary cytotoxic screening showed that all the compounds possess a good to moderate inhibitory activity against various cancer cell lines. Particularly, compound 6b bearing allyl moiety displayed a significant cytotoxic potential in comparison to standard drugs.

Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation.

6/6,7-Substituted 3-formylchromones (9a-e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a-e). However, reactions of substituted 2-anilino-3-formylchromones (15a-d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a-d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a-d) to N-phenylamides (17a-d), and 3-formylchromones (9a-e) to the corresponding thioaldehydes, is proffered. All the compounds (12a-e, 17a-d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 microg/ml) against Geotrichum candidum, better than fluconazole (MIC 09 microg/ml) and also possesses good antibacterial activity (MIC 52 microg/ml) against Shigella flexneri.