恩格列净有关物质的合成研究  

Synthesis of related substance of empagliflozin

作　　者：张金龙 ZHANG Jin-long(Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Lianyungang 222000,China)

机构地区：[1]正大天晴药业集团股份有限公司,江苏连云港222000

出　　处：《精细与专用化学品》2025年第2期33-36,共4页Fine and Specialty Chemicals

摘　　要：以葡萄糖酸-δ-内酯为起始原料,经羟基保护、缩合、酯化、还原、水解和氧化反应合成了一个新的恩格列净有关物质(S)-2-(4-(2-氯-5-((2S,3R,4R,5S,6R)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基)苄基)苯氧基)-4-羟基丁酸(简称恩格列净有关物质A),通过质谱(MS)和核磁共振(NMR)对结构进行了表征。对合成关键的还原步骤进行了优化,确定最优的反应试剂为三乙基硅烷/三氟化硼乙醚,反应溶剂为乙腈/水。A new empagliflozin related substance(S)-2-(4-(2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethy)tetrahydro-2H-pyran-2-yl)benzyl)phenoxy)-4-hydroxybutanoic acid(empagliflozin related substance A)was synthesized from glucono-lactone by hydroxyl protection,condensation,esterification,reduction,hydrolysis and oxidation.The structure was confirmed by MS and NMR.The key reduction steps of the synthesis were optimized,and the optimal reaction reagent was determined to be triethylsilane/boron trifluoride diethyl ether and the reaction solvent was acetonitrile/water.

关 键 词：恩格列净 葡萄糖酸-Δ-内酯 有关物质 合成 

分 类 号：TQ463[化学工程—制药化工]