title: Synthesis of azole nucleoside analogues of D-pinitol as potential antitumor agents.
abstract: 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 EC(50) of 11.3 and 22.6 microM, respectively, and showed much less inhibitory activity against human bladder cell lines (T(24)).
authors.affiliation: College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, People's Republic of China. trzhan@yahoo.com.cn
authors.forename: Tianrong
authors.initials: T
authors.lastname: Zhan
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001393:Azoles; D009705:Nucleosides; D014230:Triazoles; C021730:pinitol; D007294:Inositol; C012771:benzotriazole