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

• An effective procedure for the isolation of triterpenoids 1 and 2 with large amount.
• Regiospecific synthesis of new 3,5-disubstituted isoxazoles.
• The reaction times were shorter than those reported in the literature.
• Compounds were evaluated for the anti-inflammatory and anti-proliferative activities.

Maslinic acid (1) and oleanolic acid (2) were isolated from Olea europaea L. under ultra-sonication conditions with large amounts (8.5 and 3.4 mg/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.

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