文献类型：期刊文献

中文题名：达格列净的合成

英文题名：Synthesis of Dapagliflozin

作者：禹艳坤[1];冀亚飞[1]

机构：[1]华东理工大学药学院,上海200237

年份：2011

卷号：42

期号：2

起止页码：84

中文期刊名：中国医药工业杂志

外文期刊名：Chinese Journal of Pharmaceuticals

收录：CSTPCD;;北大核心:【北大核心2008】；CSCD:【CSCD2011_2012】；

语种：中文

中文关键词：达格列净;降糖药;合成

外文关键词：dapagliflozin; antidiabetic drug; synthesis

摘要：5-溴-2-氯苯甲酸经酰氯化、与苯乙醚发生付-克反应、还原羰基得5-溴-2-氯-4'-乙氧基二苯甲烷,再与2,3,4,6-四-O-三甲基硅-D-吡喃葡萄糖酸-1,5-内酯(3)缩合、异头碳羟基醚化、脱保护得2-氯-5-(1-甲氧基-D-吡喃葡萄糖-I-基)-4'-乙氧基二苯甲烷(7),然后以Et_3SiH/BF_3·OEt_2还原脱除甲氧基、乙酐酯化、水解制得降糖药达格列净,总收率约40%。
5-Bromo-2-chlorobenzoic acid was subjected to chlorination,Friedel-Crafts acylation with phenetole and then reduction with NaBH_4/AlCl_3 to give 5-bromo-2-chloro-4＇-ethoxyldiphenylmethane,which was condensed with 2,3,4,6-tetra-O-trimethylsilyl-D-glucono-1,5-lactone（3）,followed by the etherification of the hydroxyl groups at anomeric carbon and deprotection to afford 2-chloro-5-（1-methoxy-D-glucopyranose-1-yl）-4＇- ethoxydiphenylmethane（7）.Finally,an antidiabetic drug dapagliflozin was obtained via the removal of the methoxyl of 7 with Et_3SiH/BF_3·Et_2O,esterification with acetic anhydride and hydrolysis with an overall yield of about 40%.