Regiospecific synthesis by copper- and ruthenium-catalyzed azide–alkyne 1,3-dipolar cycloaddition, anticancer and anti-inflammatory activities of oleanolic acid triazole derivatives

Abstract

The oleanolic acid (1), a natural pentacyclic triterpenoid, was quantitatively isolated from pomace olive (Olea europaea L.) under ultra-sonication conditions (6.8g (3.4mg/gDW)). Two series of oleanolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester 6a–g and new oleanolic acid-1-phenyl-1H-[1,2,3]triazol-5-ylmethylester 7a–g congeners have been designed and synthesized in an attempt to develop potent anticancer and anti-inflammatory agents. A facile and regiospecific synthesis of 1,2,3-triazoles catalyzed by Cu(I) (CuAAC) or Ru(II) (RuAAC) and conducted under microwave conditions of oleanolic acid–alkyne derivative 5 with various aromatic azides 2a–g afforded a series of 1,4- and 1,5-triazolyl derivatives, respectively. Their structures were confirmed by using 1H NMR, 13C NMR, NOESY and HRMS analysis. Most of the compounds were evaluated for their anticancer and anti-inflammatory activities. Oleanolic acid 1 exhibited promising anticancer activity against murine breast (EMT-6) and human colon (SW480) cancer cells. Its derivatives 6b and 6c (1,4-regioisomers) and 7b (1,5-regioisomer) were found to be anti-cancer agents. On the other hand, only 6b displays anti-inflammatory activity.