With c-mangostin 3 in hands, the propargyl group was introduced by the mono-alkylation using propargylic bromide and potassium carbonate. Finally, with propargyl ether 17 in hands, the triazole 18 was synthesized via copper-catalyzed click chemistry, in which sodium ascorbate and copper sulfate in DMSO were treated with azidoacetate prepared in situ by the reaction of t-butyl bromoacetate and sodium azide. This developed synthetic process would be a very useful tool for a future chemical biology research to reveal a-mangostin’s target protein and its biological significance.