Looking for a new antitubercular pharmacophore site: synthesis and bioactivity of spiroheterocycles 2,3',4'-tri-subsituted-1,2-dihydro-4H,4'H-spiro[isoquinoline-3,5'-isoxazol]-4-ones

Abstract

Synthesis of a series of fourteen novel 2,3',4'-tri-subsituted-1,2-dihydro-4H,4'Hspiro[isoquinoline-3,5'-isoxazol]-4-ones was accomplished in good yield by regio and stereoselective 1,3-dipolar cycloaddition of p-R 2 -benzadoxime 4-8 with dipolarophiles (3Z)-3-The structure of the isolated products 9-23 was established through different spectroscopic techniques. X-Ray crystal structure analysis of one of the products confirms the structure and the selective region and stereochemistry of this cycloaddition. Their antitubercular activity is also evaluated.

Facial selectivity induced by N-aryl atropisomerism in benzonitrile oxide cycloadditions with 4-methylene-2-oxazolidinones

“…Atropisomerism is a relatively overlooked source of asymmetry, with important implications in the pharmaceutical industry. 19 This phenomenon, in relation to facial selectivity of NOC reactions, had remained unnoticed in the field because previously reported NOC reactions on methylene N-substituted heterocycles, [20][21][22][23] including by us, 8 had all used symmetrical or non-hindered N-substituents.…”