恩替卡韦的合成  

Synthesis of Entecavir

作　　者：杨守宁[1] 张磊 胡文浩[1] 杨琍苹[1] 

机构地区：[1]华东师范大学化学系,上海200062 [2]上海清松制药有限公司,上海201417

出　　处：《中国医药工业杂志》2013年第7期657-659,共3页Chinese Journal of Pharmaceuticals

摘　　要：(1S,2S,3S,5S)-3-苄氧基-5-[6-苄氧基-2-[(三苯甲基)氨基]-9H-嘌呤-9-基]-2-[(苄氧基)甲基]环戊醇在碳酸氢钠作用下先被TEMPO/碘氧化,所得产物再与由镁/四氯化钛/二氯甲烷/THF形成的亚甲基化体系反应生成(1S,3R,4S)-N-(三苯甲基)-6-苄氧基-9-[[2-亚甲基-4-苄氧基-3-(苄氧基)甲基]环戊基]-9H-嘌呤-2-胺(4),在三氯化硼/甲醇/水的作用下脱除保护基制得恩替卡韦,总收率约44%。Entecavir was synthesized from （1S,2S,3S,5S）-3-benzyloxy-5-[6-benzyloxy-2-（tritylamino）-9H-purin-9-yl]-2-（benzyloxymethyl）-cyclopentanol by oxidation with TEMPO/I2 in the presence of NaHCO3, and methylenation with Mg/TiCl4/DCM/THF to give （1S,3R,4S）-N-triphenylmethyl-6-benzyloxy-9-[[2-methylene-4- benzyloxy-3-（benzyloxy）methyl]cyclopentyl]-9H-purin-2-amine（4）, which was subjected to deprotection with BCl3/MeOH/H2O with an overall yield of about 44%.

关 键 词：恩替卡韦 抗乙肝病毒药 合成 

分 类 号：R978.7[医药卫生—药品]