Synthesis and evaluation of Calenduloside E against drug-resistant Candida albicans

Calenduloside E (CE), also known as a triterpenoid saponin, has demonstrated diverse biological activities. This paper investigates the chemical synthesis of CE, focusing on the key step of glucuronidation of oleanolic acid benzylate. Among trichloroacetimidate, bromide, and thioglucuronide as glucuronyl donors, trichloroacetimidate proved most effective, with scandium(III) trifluoromethanesulfonate identified as the optimal promoter. Notably, CE exhibited significant activity against fluconazole-resistant C. albicans (ATCC14053), with an MIC₈₀ of 5.5 µg/ml. Further mechanistic studies demonstrated that the combination of CE and FLC significantly inhibits the proliferation of C. albicans hyphae, biofilm formation, and cell membrane function.