新颖的SGLT2抑制剂奥洛格列净的合成路线选择与工艺研发  

Synthesis Route Selection and Process Development of a Novel SGLT2 Inhibitor Olorigliflozin

作　　者：顾峥 伍武勇 李峥 张宗远 吴天云 张霁[1,2] GU Zheng;WU Wuyong;LI Zheng;ZHANG Zongyuan;WU Tianyun;ZHANG Ji(HEC Pharmaceutical Research Institute,HEC Pharm Group,Dongguan 523871;State Key Lab.of Anti-Infective Drug Discovery and Development,Sunshine Lake Pharma Co.,Ltd.,Dongguan 523871)

机构地区：[1]广东东阳光集团药业研究院,广东东莞523871 [2]广东东阳光药业,抗感染新药研发全国重点实验室,广东东莞523871

出　　处：《中国医药工业杂志》2025年第2期170-180,共11页Chinese Journal of Pharmaceuticals

基　　金：重大新药创制科技重大专项“十三五”计划项目(2018ZX09301007005)。

摘　　要：文章分析、总结了新颖的钠-葡萄糖耦联转运体2(SGLT2)抑制剂奥洛格列净(1)的合成策略、工艺研发和路线选择。根据原料不同,可分为路线一(以吡喃糖中间体A-1为原料合成1)和路线二(以开环中间体B-1为原料合成1)。其中,根据可分离中间体数量的不同,又可将路线二分为路线①和路线②。合成B-1的路线②(10步反应)通过筛选合适的保护基,避免了危险试剂的使用和超低温反应,更易通过叠缩工艺实现分离、纯化。路线②的总收率为24.2%,纯度为99.72%。该路线质量可控,立体选择性高,适用于工业化生产,目前已成功制备公斤级以上规模的1。Olorigliflozin(1)is a novel sodium-glucose linked transporter 2(SGLT2)inhibitor.Its synthesis strategies,process development and route selection were analyzed and summarized.According to the different raw materials,there were route one(pyranose intermediate A-1 was used for the synthesis)and route two(ring-opening intermediate B-1 was used for the synthesis)for the overall synthesis of 1.And route two could be divided into route①and route②according to the amount of separatable intermediates.By screening suitable protecting groups,the route②(10 steps)avoided the use of hazardous reagents and ultra-low temperature reactions,which was more easily to separate and purify through the telescopingprocess.The total yield of the roud②was 24.2%with the purity of 99.72%.This route hold controllable quality and highstereoselectivity,which is suitable for industrial production.At present,it has successfully prepared 1 in kilograms and above.

关 键 词：奥洛格列净 降血糖药 钠-葡萄糖耦联转运体2抑制剂 糖尿病 工艺研发 合成路线 

分 类 号：TQ460.6[化学工程—制药化工]