脱苏氨醇奥曲肽的微波辅助合成  

Microwave-assisted Synthesis of [des-Thr-ol^8]-Octreotide

作　　者：杨潇骁[1] 林浩[1] 王德心[1] 

机构地区：[1]北京协和医学院中国医学科学院药物研究所,北京市活性物质发现与适药化研究重点实验室,北京100050

出　　处：《中国医药工业杂志》2012年第9期729-733,共5页Chinese Journal of Pharmaceuticals

摘　　要：利用自制100 ml微波反应管通过微波辅助固相肽合成技术制得奥曲肽原料药中关键有关物质脱苏氨醇奥曲肽(1)。采用Fmoc策略以2-Cl-Trt-树脂为固相载体,经上载、缩合、脱保护、裂解等操作合成还原型脱苏氨醇奥曲肽,再用空气氧化法并加入活性炭快速氧化得到1,总收率62.9%,单批次产量达3.5 g,中间体及终产物经高分辨质谱及氨基酸分析确证,并通过圆二色谱法研究了环合前后多肽构象的变化。该方法比传统固相合成方法快捷,为研究奥曲肽的关键有关物质提供了可行的合成方法。[des-Thr-ol^8]-Octreotide（1）, a major related substance of octreotide, was successfully synthesized with 100 ml reaction tube made from centrifuge tube by microwave-assisted solid phase stepwise synthesis technique in pilot scale. Synthesis was carried out with 2-C1-Trt resin by Fmoc strategy. After cleavage of the resin, linear peptide was oxidized in aqueous solution by air in the presence of active carbon and purified by preparative RP-HPLC subsequently to give the target peptide 1 in 62.9 % overall yield with excellent purity. The compound 1 was confirmed by HRMS and amino acid analysis, and the conformation change between linear and cyclic peptide was investigated by CD spectra.

关 键 词：脱苏氨醇奥曲肽 微波 合成 二硫键 

分 类 号：R979.9[医药卫生—药品] O629.72[医药卫生—药学]