Merrifield树脂在改构肽合成中的新应用  

New Application of Merrifi eld Resin in the Synthesis of Structural Modifi ed Peptides

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》2014年第6期519-524,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金(81001366);药物研究所科研基金(2012CHX12)

摘　　要：本文介绍的正交杂化合成策略(HOP)采用以Merrifield树脂为载体,将Fmoc化学与Boc化学结合应用组装多肽,经酸解脱除侧链保护基得到键合在树脂上的裸肽树脂中间体,并进一步经温和、简便的胺解反应,衍生出多肽C末端N-取代酰胺或侧链内酰胺环肽化合物。HOP策略得到的终产物粗制品中不含有常规工艺的酸解试剂等杂质,所以采用该方式合成肽酰胺在收率及粗产物纯度等方面均比较理想。Based on Merrifield resin,a new strategy,HOP （hybrid orthogonal protocol）,was explored.In this strategy,Fmoc protocol and Boc protocol were matched on Merrifield resin in one batch synthesis.By this way the key intermediate,naked peptidyl-resin,could be prepared just after TFA treatment which removed side-chain protecting groups （tBu,Trt,Boc,Pbf...）,but the peptidyl-resin linkage was retained.Based on the naked peptidyl resin,different kinds of products with C-terminal N-substituted peptide amides and side-chain lactam bonding cyclopeptides could be easily produced with more reasonable yields and purities than that from conventional protocol of SPPS.

关 键 词：Merrifield树脂 HOP策略 固相肽合成 肽结构改造 

分 类 号：O629.72[理学—有机化学]