Synthesis, characterization and biological studies of some heterocyclic and aromatic substituted Isoxazoli(DI)nes

Abstract

In the present work, we have synthesized five membered heterocyclic isoxazoli(di)nes newlinevia 1,3-dipolar cycloaddition reaction. The key intermediate 1,3-dipole nitrones, were newlinesynthesized by in situ generation of hydroxylamine through the control reduction of newlinenitroarenes. newlineSynthesized trimethoxyphenyl isoxazolidine derivatives are good inhibitors of the PLA2 newlineenzyme. The inhibition of isoxazolidine derivatives was further enhanced by newlinesubstituting hydrophobic and aromatic groups in the 5th position of the ring, which is newlineessential for binding at the catalytic domain of the enzyme. As the in vitro inhibition of newlinethe enzyme by these isoxazolidine derivatives correlated well with the in vivo inhibition newlineof the edema-inducing activity, these derivatives are therapeutically important as antiinflammatory newlinedrugs. newlineThe imidazolyl isoxazolidines were synthesized and screened antimicrobial inhibition. newlineWe observed some of those were potent towards antifungal than antimicrobial activity. newlineFurther, to enhance the activity we have synthesized 96% ee pure isoxazolidine using newlinechairal catalyst. 2D-NMR (COSY, HMBC, HMQC and DEPT) experiments for 3-(2-butyl- newline4-chloro-1H-imidazolyl)-2,5-diphenyl isoxazolidine has done and confirms that, 5- newlinesubstituted product is stable than 4-subtituted. newline5-substituted isoxazoline derivatives of the tricyclic azepine were synthesized and the newlineregioisomer of the product has characterized using 1D and 2D NMR. The study revealed newlinethat, steric hindrance is the key factor to form 5-substituted isoxazoline product. newlineIntramolecular 1,3 dipolar cycloaddition reaction of 1-allyl-2-butyl-4-chloro-1Himidazole- newline5-carboxaldehyde and phenyl hydroxylamine leading to piperidine tricyclic newlineimidazole isoxazolidine with high stereoselective than pyrrolidine tricyclic imidazole newlineisoxazolidine. The detailed structural confirmation was done using 1D and 2D (COSY, newlineHMBC, HMQC and NOESY) experiments.