阿拉莫林的合成工艺研究  

Study on the synthetic process of anamorelin

作　　者：关雨晴 袁瑜 黄波 罗进文 鲁晓莉 孟广鹏 周琳 GUAN Yu-qing;YUAN Yu;HUANG Bo;LUO Jin-wen;LU Xiao-li;MENG Guang-peng;ZHOU Lin(Chengdu Sintanovo Biotechnology Co.,Ltd.,Chengdu 610000,China;College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 610000,China;Chengdu Institute For Drug Control,Chengdu 610045,China)

机构地区：[1]成都诺和晟泰生物科技有限公司,四川成都610000 [2]成都中医药大学药学院,四川成都610000 [3]成都市药品检验研究院,四川成都610045

出　　处：《中国药物化学杂志》2023年第5期362-366,共5页Chinese Journal of Medicinal Chemistry

摘　　要：目的 优化阿拉莫林的合成工艺。方法 以(R)-3-苄基-1-(叔丁氧基羰基)哌啶-3-甲酸(2)和N,N,N′-三甲基肼为起始原料,经缩合、脱保护反应循环3次,得到目标化合物阿拉莫林。其中,偶联Boc-D-Trp-OH的缩合体系为HOOBt-EDCI-TEA,偶联Boc-Aib-OH的缩合体系为TBTU-DIEA。结果与结论目标化合物的结构经MS、1H-NMR谱确证,总收率为69%(以化合物2计),纯度为99.5%(HPLC法)。该合成路线原料易得、操作简单、产物纯度高,适合大规模工业化生产。An improved synthetic process of anamorelin was reported.(R)-3-benzyl-1-(tert-butyloxyl carbonyl)-piperidine-3-formic acid(2) and N,N,N′-trimethylhydrazine were used as starting materials.The targeted compound was afforded by condensation, deprotection, condensation, deprotection, condensation and deprotection.The condensation system of coupling with Boc-D-Trp-OH was HOOBt-EDCI-TEA and the condensation system of coupling with Boc-Aib-OH was TBTU-DIEA.The structure of anamorelin was confirmed by MS and 1H-NMR.The overall yield was up to 69%(based on compound 2) with the HPLC purity of 99.5%.The improved synthetic process has the advantages of available raw materials, simple operation, and high purity, which is suitable for large-scale industrial production.

关 键 词：阿拉莫林 生长激素促分泌素受体激动剂 癌症恶病质 合成工艺 

分 类 号：R914[医药卫生—药物化学]