2型糖尿病治疗药西他列汀的合成研究  

Synthesis of an anti-type 2 diabetes mellitus drug,sitagliptin

作　　者：吴婷[1] 刘媛[2] 东鸿鑫 夏超[2] 石金城[2] 

机构地区：[1]南京工业大学药学院,南京210009 [2]江苏省药物研究所有限公司,南京210009

出　　处：《中国新药杂志》2015年第21期2499-2501,2510,共4页Chinese Journal of New Drugs

摘　　要：目的:研究西他列汀合成的新工艺。方法:以2,4,5-三氟苯乙酸为原料,与麦氏酸缩合,然后与NH2-BOC缩合,通过不对称还原反应得到西他列汀关键手性中间体(R)-3-(叔丁氧羰基氨基)-4-(2,4,5-三氟苯基)丁酸。最后与3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-α]吡嗪盐酸盐中间体缩合,脱保护,成盐得到终产物西格列汀。结果:以总收率36%合成西他列汀。结论:该合成路线具有步骤少、操作简便、收率高、立体选择性好、反应条件温和的特点。Objective： To study the synthesis process of sitagliptin. Methods： The chiral intermediate（ R）-3-amino-4-（ 2,4,5-trifluoro-phenyl）-butyric acid was synthesized from 2,4,5-trifluoro-phenyl acetic via condensation with Meldrum＇s acid,condensation with NH2-Boc,followed by asymmetric reduction. The target compound sitagliptin was obtained from the key chiral intermediate via condensation with 3-（ trifluoro methyl）-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride. Results： The total yield came up to 36%. Conclusion： The synthetic route has characteristics of minimal steps,simple-operation,high total yield,good stereoselectivity and mild condition.

关 键 词：西他列汀 2型糖尿病 不对称还原 

分 类 号：R914.5[医药卫生—药物化学]