非天然氨基酸PMP的合成工艺研究  

Research on Synthesis Process of Unnatural Amino Acid PMP

作　　者：王晨露 杜章宁 吴伟平 郑苏欣 周银建 熊兵 池岛乔[1] WANG Chenlu;DU Zhangning;WU Weiping;ZHENG Suxin;ZHOU Yinjian;XIONG Bing;CHI Daoqiao(College of Wuya Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Hanhai(Nantong)Biotechnology Co.,Ltd.,Nantong 226133,China;Jishan Biotechnology(Suzhou)Co.,Ltd.,Suzhou 215028,China;Suzhou Institute for Biomedical Research,Suzhou 215028,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016 [2]中国科学院上海药物研究所,上海201203 [3]晗海(南通)生物科技有限公司,江苏南通226133 [4]霁山生物科技(苏州)有限公司,江苏苏州215028 [5]苏州生物医药转化工程中心,江苏苏州215028

出　　处：《山东化工》2025年第2期51-54,共4页Shandong Chemical Industry

摘　　要：目的:报道一种简便易行、安全、低毒的2-氨基-3-(4-(膦酰基甲基)苯基)丙酸(PMP)制备方法。方法:以(S)-2-氨基-3-(对甲苯基)丙酸为起始原料,在SOCl2/MeOH作用下反应得到(S)-2-氨基-3-(对甲苯基)丙酸甲酯。经乙酰氯酰基化后得到化合物(S)-2-乙酰氨基-3-(对甲苯基)丙酸甲酯,随后在乙腈溶液中,在偶氮二异丁腈(AIBN)的参与下与N-溴代丁二酰亚胺(NBS)反应得到(S)-2-乙酰氨基-3-[4-(溴甲基)苯基]丙酸甲酯,然后在三乙基亚磷酸酯中反应得到(S)-2-乙酰氨基-3-{4-[(二乙氧基磷酰基)甲基]苯基}丙酸甲酯,最后在9 mol/L HCl中回流16 h后水解、后处理得到游离的PMP。结果:本方法中,目标化合物的合成不仅避免了使用剧毒化合物(氯甲基甲醚氯),且总收率为68%,相比现有文献报道方法有较明显提高。结论:合成所需原料廉价易得,纯化过程简单高效,因而方便推广和普及,具有较高的商业化价值。Objective:A novel and safer synthetic preparation procedure for 2-amino-3-(4-(phosphonomethyl)phenyl)propanoic acid(PMP)was investigated.Methods:Methyl(S)-2-amino-3-(p-tolyl)propanoate was synthesized by reacting of SOCl 2/MeOH with(S)-2-amino-3-(p-tolyl)propionic acid,and then methyl(S)-2-acetamido-3-(p-tolyl)propanoate was acylated by acetyl chloride.Methyl(S)-2-acetamido-3-(4-(bromomethyl)phenyl)propanoate was prepared in the presence of N-bromosuccinimide(NBS)and 2,2'-azobis(2-methylpropionitrile)(AIBN)in acetonitrile(ACN).Subsequently,methyl(S)-2-acetamido-3-(4-((diethoxyphosphoryl)methyl)phenyl)propanoate was obtained by reacting with triethyl phosphite,which was then deprotected under refluxing in 9 mol/L HCl for 16 h to obtain free PMP.Results:This PMP synthetic strategy avoided the application of highly toxic compound(chloromethyl methyl ether chloride)with the higher yield of 68%at the same time.Conclusion:The novel synthetic procedure endow the development of PMP with high commercial value.

关 键 词：(S)-2-氨基-3-[4-(膦酰甲基)苯基]丙酸 非天然氨基酸 酪氨酸磷酸化 

分 类 号：TQ241.1[化学工程—有机化工]