Regiospecific synthesis, anti-inflammatory and anticancer evaluation of novel 3,5-disubstituted isoxazoles from the natural maslinic and oleanolic acids

摘要

Maslinic acid (1) and oleanolic acid (2) were isolated from Olea europaea L. under ultra-sonication conditions with large amounts (8.5 and 3.4mg/g DW, respectively). Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between natural pentacyclic triterpenoid-alkyne derivatives and a series of aryl nitrile oxides, regiospecifically afforded 3,5-disubstituted isoxazoles in quantitative yields. The reaction times were shorter than those reported in the literature. Most of the compounds were evaluated for their anti-inflammatory and anti-proliferative activities. Compounds 12c, 12e, 12g, 13c and 13d found to have higher anti-inflammatory activity. The anti-proliferative evaluation towards EMT-6 and SW480 cancer cell lines indicated that most of the compounds exhibited significant anti-cancer activity. Among all triterpenic derivatives, isoxazole 12g bearing a furfuryl ring in its isoxazole moiety was found to have highest anti-inflammatory and anti-cancer activity. Therefore, this derivative can serve as a promising lead candidate for further study. (C) 2016 Elsevier B.V. All rights reserved.