保护氨基酸Fmoc-His(Trt)-OH的合成方法优化  

Synthesis and Optimization of Protected Amino Acid Fmoc-His(Trt)-OH

作　　者：赵萍萍[1] 徐大刚[1] 廖晓全[1] 杜晓宁[1] 李良君[1] 

机构地区：[1]上海化工研究院,上海200062

出　　处：《化学世界》2008年第9期549-552,共4页Chemical World

基　　金：上海市科委科研计划项目经费资助:06DZ113034;06DZ22207

摘　　要：在肽合成中,为了得到理想的目的肽,首先需要对氨基酸的活性基团加以封闭或保护。叔丁氧羰基(Boc)和9-芴甲氧羰基(Fmoc)是固相合成中首选的-αNH2保护基,由此形成了多肽固相合成方法中的两大类:Boc方法和Fmoc方法。组氨酸(His)是多肽合成中问题最大的氨基酸之一,需要对其α-氨基及侧链上的咪唑环加以保护。由于Fmoc保护基的一些独特优点,如对碱的不稳定性、易检测性等,因此,我们选择Fmoc为其-αNH2保护基。在Fmoc策略合成过程中,三苯甲基(Trt)对缩合以及脱保护条件都很稳定,它可被稀乙酸在稍高的温度条件下,或TFA在室温脱除,因而选用Trt封闭咪唑环上的活性官能团。实验通过中心曲面实验设计方法和正交实验设计方法对His的两步保护反应条件进行优化,使得最终两步反应收率分别都达到80%以上,产品纯度达到95%以上。For the purpose of gaining perfect peptide, it was necessary to block or protect the active groups first. In the solid peptide synthesis, Boc and Fmoc were the preferred α-NH2 protective groups. The two main ways of solid peptide synthesis- Boc strategy and Fmoc strategy were formed. Histidine （His） was one of the most difficult amino acid in peptide synthesis, so its α-NH2 and imidazole ring must be protected. Because of Fmoc group＇s some specific virtues,like its instability to alkali and the nature of easy to be detected, we chose Fmoc as the α-NH2 protecting group. In Fmoc strategy, trityl was stable to the conditions of coupled action and＇deprotection. It can be removed by dilute acetic acid at tallish temperature, or by TFA at room temperature. So we chose Trt as the side-chain protecting group. With the methods of central composite design and orthogonal design, the final optimized conditions were obtained,and the yields of the two steps reached above 80% respectively. The purity was above 95%.

关 键 词：纽氨酸(His) 氨基酸保护 三苯甲基(Trt) 9-芴甲氧羰基(Fmoc) 

分 类 号：O629.71[理学—有机化学]