Synthesis of azole nucleoside analogues of d-pinitol as potential antitumor agents

A convenient strategy is reported for the synthesis of azole nucleoside analogues of d-pinitol (=3-O-methyl-d-chiro-inositol). The key intermediate 3-O-methyl-4,5-epoxy-d-chiro-inositol was obtained in excellent yield via an epoxidation from mono-methanesulfonate of d-pinitol. The process of opening of the epoxy ring by azole-bases appeared strongly regioselective in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene. All newly synthesized carbocyclic azole nucleosides were assayed against lung and bladder cancer in vitro. Only the triazole and benzotriazole nucleoside analogues inhibited the growth of human lung cancer cell lines (PG) with EC50 of 11.3 and 22.6 μM, respectively, and showed much less inhibitory activity against human bladder cell lines (T24).