氮苷1-(2,′3,′4,′6′-O-四乙酰基-β-D-吡喃葡萄糖基)-咪唑的制备

以D-葡萄糖(Ⅰ)、醋酸酐为原料,在无水吡啶中制得中间体1,2,3,4,6-O-五乙酰基-D-葡萄糖(Ⅱ),收率为87.5%。在HB r/CH3COOH条件下对Ⅱ异头碳上的乙酰基进行溴代,制得1-溴-2,3,4,6-O-四乙酰基-D-葡萄糖(Ⅲ),不经分离,在相转移催化剂TEBA催化下,Ⅲ直接与2,4-二硝基苯酚反应得到酚苷1-O-(2,′4′-二硝基苯)-2,3,4,6-O-四乙酰基-β-D-葡萄糖苷(Ⅳ),最后Ⅳ与1-三甲基硅基-咪唑在无水四氯化锡的催化下,室温反应52 h制得氮苷1-(2,′3,′4,′6′-O-四乙酰基-β-D-吡喃葡萄糖基)-咪唑(Ⅴ),此步反应收率为90%。

Synthesis of 1-(2′,3′,4′,6′-Tetra-O-acetyl-β-D-glycopyranosyl)-imidazolenucleoside

Starting from D-glucose(Ⅰ)and acetic anhydride,in the presence of anhydrous pyridine,the intermediate 1,2,3,4,6-penta-O-acetyl-β-D-glucose(Ⅱ) was obtained in 87.5% yield.Treating Ⅱ with HBr/CH_3COOH gave the compound 2,3,4,6-tetra-O-acetyl-β-D-glycopyranosyl bromide(Ⅲ).Without purification,using TEBA as phase transfer catalyst,Ⅲ reacted directly with 2,4-dinitrophenol to give the phenolic glycoside 1-O-(2′,4′-dinitrophenyl)-2,3,4,6-tetra-O-acetyl-β-D-glucoside(Ⅳ).Finally,by reaction of Ⅳ and trimethylsilylimidazole with anhydrous SnCl_4 as catalyst under room temperature for 52 h,1-(2′,3′,4′,6′-tetraO-acetyl-β-D-glycopyranosyl)-imidazolenucleoside(Ⅴ)was synthesized in about 90% yield.