- 作者: 王英基 ; 陳豪勇 ; 曾誠齊
- 作者服務機構: 高雄醫學院化學系
- 中文摘要: 3'-Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5), prepared from epichlorohydrin and sodium benzyloxide, underwent ring opening by soft halogen ions to give 1- benzyloxy-3-fluoro-2-propanol (6), 1-benzyloxy-3-chloro-2- propanol (7), and 1-benzyloxy-3-bromo-2-propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1-benzyloxy-3-iodo-2- propanol (9). The treatment of 8 with sodium iodide in anhydrous acetone also produced 1-benzyloxy-3-iodo-2- propanol (9). Chloromethylation of these halohydrins 6-9 using paraformaldehyde and hydrogen chloride gas produced the chloromethyl ethers 10-13. These chloromethyl ethers without further purification were allowed to react with the silylated bases 16-17, previously prepared by silylating the bases 14-15 with HMDS in the presence of ammonium sulfate to give 1- [ (1-benzyloxy-3-halogen-2-propoxy)methyl ] uracils and thymines 19-25. The target compounds 26-33 were obtained respectively after the debenzylation of 18-25. Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001-20mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20mM.
- 英文摘要: --
- 中文關鍵字: Acyclonucleoside; Antiviral Activity; Chloromethylation; Benzyl Glycidyl Ether; 1-Benzyloxy-3-Fluoro-2-Propanol; Halohydrin
- 英文關鍵字: 環核類;抗病毒活性;氯甲基化反應;苯甲基環氧丙酯乙醚;1-氧-3-氟-2-丙醇;鹵氫化物