Synthesis and antifungal activity of novel oxazolidin-2-one-linked 123-triazole derivatives

摘要

Novel oxazolidin-2-one-linked 1,2,3-triazole derivatives (>4a–k) were synthesized by straightforward and versatile azide–enolate (3 + 2) cycloaddition. The series of compounds was screened for antifungal activity against four filamentous fungi as well as six yeast species of Candida spp. According to their efficiency and breadth of scope, they can be ordered as >4k > >4d > >4h > >4a, especially in relation to the activity displayed against Candida glabrata ATCC-34138, Trichosporon cutaneum ATCC-28592 and Mucor hiemalis ATCC-8690, i.e. compounds >4d, >4h and >4k showed excellent activity against C. glabrata (MIC 0.12, 0.25 and 0.12 μg mL^–1, respectively), better than that of itraconazole (MIC 1 μg ml^–1). The activity of compound >4d (MIC = 2 μg mL^–1) was higher than that observed for the standard antifungal drug (MIC = 8 μg mL^–1) against Trichosporon cutaneum, while compound >4k displayed an excellent antimycotic activity against Mucor hiemalis (MIC = 2 μg mL^–1vs. 4 μg mL^–1 for itraconazole). In addition, we describe herein a novel mild and eco-friendly synthetic protocol for obtaining β-ketosulfones (adducts to afford compounds >4a–k) from α-brominated carbonyls in an aqueous nanomicellar medium at room temperature.