微波作用下醋酸亮丙瑞林的固相合成  

Solid phase synthesis of leuprorelin under microwave irradiation

作　　者：张俊[1] 岑涛[1] 王安明[1] 周成[1] 杜志强[1] 武秀明[1] 沈树宝[1] 

机构地区：[1]南京工业大学制药与生命科学学院材料化学工程国家重点实验室,江苏南京210009

出　　处：《化学试剂》2009年第6期401-404,共4页Chemical Reagents

基　　金：国家自然科学基金资助项目(20376034);十一五国家863资助项目(2006AA02Z211);江苏省自然科学基金项目(BK2006181);江苏省高校研究生创新计划项目(2007)

摘　　要：在醋酸亮丙瑞林的固相合成中引入微波技术,深入研究了大位阻氨基酸Fmoc-Arg(Pbf)-OH与H-Pro-CTC树脂(CTC树脂:2-氯三苯甲基氯树脂)的缩合反应。反应的最优条件为以V(DMF)∶V(NMP)∶V(THF)=1∶1∶1为溶剂,HBTU为缩合试剂,21 mmol/L氨基酸、微波辐射3 min、反应温度35℃、维持时间6 min,Fmoc-Arg(Pbf)-OH与H-Pro-CTC树脂的缩合率达到84.7%。最终标题化合物的产率达到81.3%。A microwave-irradiation technique was applied to the solid phase synthesis of leuprorelin. The coupling reaction of Fmoc-Arg（Pbf）-OH known as a sterically hindered amino acid with H-Pro-CTC Resin （CTC resin,2-chlorotrityl chloride resin） was investigated. The optimal conditions were as foUows： DMF/ NMP/THF （at a ratio of 1 ： 1 ： 1 by volume） was used as the solvent, HBTU was used as the coupling reagent, the concentration of amino acids was 21 retool/L, the microwave irradiation time was 3 rain, and the reaction temperature was 35 ℃, which was maintained for 6 min. The yield of the target product after coupling of Fmoc-Arg （Pbf）-OH with the H-Pro-CTC resin was improved to reach 84.7 % . Finally, the yield of leuprorelin reached 81.3 % under optimal conditions.

关 键 词：微波 固相多肽合成 亮丙瑞林 大位阻氨基酸 

分 类 号：TQ464.7[化学工程—制药化工]