索格列净的合成研究进展  

Recent Progress of Synthesis of Sotagliflozin

作　　者：陈东蕾 焦雪 王悦 蔡爽 郑璐 CHEN Donglei;JIAO Xue;WANG Yue;CAI Shuang;ZHENG Lu(Key Lab.of Active Molecular Screening for Marine Drugs in Jiangsu Province,College of Pharmacy,Jiangsu Ocean University,Lianyungang222005)

机构地区：[1]江苏海洋大学药学院,江苏省海洋药物活性分子筛选重点实验室,江苏连云港222005

出　　处：《中国医药工业杂志》2025年第2期147-154,共8页Chinese Journal of Pharmaceuticals

基　　金：江苏省大学生创新创业训练计划项目(SY202311641640011)。

摘　　要：索格列净(1)是一种可口服的钠-葡萄糖耦联转运体l和2(SGLT-l和SGLT-2)抑制剂,临床上主要用来治疗糖尿病。1的化学结构包含5个连续手性中心的糖基部分、1个芳基疏水片段和1个甲硫醚基团。通过逆合成分析可知,1的合成有3个重点:①手性中心的构建;②芳基片段与糖基的连接;③甲硫基的引入。因此,该研究从起始原料,即不同的糖基手性中心构建原料,对1的合成路线进行总结,归纳了以L-木糖为起始原料的5条合成路线、以L-葡萄糖为起始原料的1条合成路线和以达格列净乙酸酯为起始原料的1条路线,并对各路线进行了简要评述,期望为其合成工艺研究提供一定的参考。Sotagliflozin(1) is an oral inhibitor of sodium-dependent glucose transporters 1 and 2(SGLT-l and SGLT-2),which is clinically used to treat diabetes mellitus.The chemical structure of 1 is composed of one sugar moiety with five chiral centers,one aryl hydrophobic fragment and one methyl sulfide group.According to the analysis ofreverse synthesis,the synthesis of 1 is focused on three key points:①the construction of chiral center;②coupling of aryl fragments with sugar groups;③introduction of the methylthio group.Based on the construction of glycosyl chiral centers,herein the synthetic routes of 1 are summarized from the different starting materials for the construction of glycosyl chiral centers.Five synthetic routes using L-xylose as the starting material,one route with using L-glucose,and one route withdapagliflozin acetate as the starting material are reviewed and discussed,which provides some references for the researches on the synthesis.

关 键 词：索格列净 糖尿病 降血糖药 合成 研究进展 

分 类 号：R977.15[医药卫生—药品] TQ460.6[医药卫生—药学]