基于连续流动化学的Bivalirudin绿色合成方法的研究  

Green synthesis of Bivalirudin by continuous flow chemistry

作　　者：王振炜 刘豪 黄鼎旻 苏贤斌 WANG Zhen-wei;LIU Hao;HUANG Ding-min;SU Xian-bin(College of Chemical Engineering,Qingdao University of Science and Technology,Qingdao 266042,China;College of Chemical Engineering,Nanjing Tech University,Nanjing 210009,China)

机构地区：[1]青岛科技大学化工学院,山东青岛266042 [2]南京工业大学化工学院,江苏南京210009

出　　处：《现代化工》2023年第11期140-144,149,共6页Modern Chemical Industry

基　　金：省部共建生态化工协同创新中心人才基金资助(1203042904001419)。

摘　　要：提出了一种新型绿色多肽合成方法,并成功将该方法应用于水蛭素的二十肽类似物Bivalirudin的合成。以苄氧羰基(Cbz)为氨基保护基,利用钯炭装填柱快速脱去Cbz保护,偶联反应及其后处理在微通道反应器内完成,实现了偶联-后处理-脱保护全体系的连续化。结果表明,相比于传统多肽合成方法,该方法原子经济性高、环境污染小,有望在多肽合成产业中得到更加广泛地应用。A novel green peptide synthesis method is proposed,and successfully applied to the synthesis of Bivalirudin,an icosapeptide analogue of hirudin.Benzyloxycarbonyl(Cbz)is used as a protecting group for amino,while the protection is rapidly removed in a column packed with Pd/C catalyst.The coupling reaction and its post-treatment are finished in a microchannel reactor via continuous flowing process,which achieves the continuity of the coupling-posttreatment-deprotection system.It is verified that this method shows a higher atom economy and fewer environment pollution than traditional peptide synthesis methods,it is expected to be more widely used in the peptide synthesis industry.

关 键 词：连续流动化学 微通道反应器 比伐芦定 多肽合成 

分 类 号：TQ464.7[化学工程—制药化工] O629.72[理学—有机化学]