保护氨基酸Fmoc_His_Trt_OH的合成方法优化_赵萍萍.pdfVIP

9 　　　　　　 　 ·549 · Fmoc-His (Trt)-OH , 　, 　, 　, 　 ( 200062) 　: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。 丁氧羰基(Boc)和9-芴甲氧羰基(Fmoc)是固相合成中首选的α-NH2 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α-NH2 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T rt 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。 :组氨酸(His);氨基酸保护;三苯甲基(Trt);9-芴甲氧羰基(Fmoc) :O 629.71　　　:A :0367-6358(2008)09-549-04 Synthesis and O timization of Protected Amino Acid Fmoc-His(T rt)-OH ZHAO Ping-ing, 　XU Da-gang, 　LIAO Xiao-quan, 　DU Xiao-ning, 　LI Liang-jun (S han ghai R esea rch I nsti tu te of Chemi cal I nd ustry , S han ghai 200062, Chi na) Abstract:For the ur ose of gaining erfect e tide, it w as necessary to block or rotect the active grou s first.In the solid e tide synthesis, Boc and Fmoc w ere the referred α-N H2 rotective grou s.The tw o main w ays of solid e tide synthesis———Boc strategy and Fmoc strategy were formed.Histidine (His)w as one of the most difficult amino acid in e tide synthesis, so its α-NH2 and imidazole ring must be rotected.Because of Fmoc grou ssome s ecific virtues, like its instability to alkali and the nature of easy to be detected, w e chose Fmoc as the α-N H2 rotecting grou .In Fmoc strategy, trityl w as stable to the conditions of cou led action and de rotection.It can be removed by dilute acetic acid at tallish tem erature, or by TFA at room tem erature.So w e chose T rt as the side-chain rotecting grou .With the methods of central com osite design and orthogonal design, the final o timized conditions w ere obt