高苯丙氨酸的合成新工艺研究  

Study on a new process for the synthesis of homophenylalanine

作　　者：张婷[1] 徐时良[1] 李景华[1] 

机构地区：[1]浙江工业大学药学院,浙江杭州310032

出　　处：《浙江工业大学学报》2011年第3期264-267,共4页Journal of Zhejiang University of Technology

摘　　要：高苯丙氨酸为非天然氨基酸,是合成血管紧张转化酶(ACE)抑制剂以及其他药物的重要中间体.研究了以苯乙酮为原料与草酸二乙酯缩合,再与醋酸铵进行氨化反应,最后在钯炭催化下进行氢化还原得到高苯丙氨酸的新工艺.较佳反应条件是:(1)缩合反应,将新制的乙醇钠滴加到溶有苯乙酮以及草酸二乙酯的甲苯溶液中且n(苯乙酮)∶n(草酸二乙酯)=1∶1.5;(2)氨化反应,采用用机械研磨的固相合成方法;(3)氢化还原反应,在高压釜中(5 MPa,90℃)进行得到目标产物.在较佳工艺条件下,反应总收率达87%以上.产品及重要中间体结构经核磁共振确认.该过程所用原料廉价、反应高效、绿色.Homophenylalanine is an unnatural amino acid which could be used in the synthesis of angiotensin converting enzyme inhibitors and other pharmaceuticals.It has been synthesized via condensation of acetophenone with diethyl oxalate,amination with NH4OAc,and reduction with hydrogen catalyzed by Pd/C.The optimum conditions were as follows：（1） condensation reaction by adding fresh NaOEt to the mixture of acetophenone and diethyl oxalate with the molar ratio of acetophenone to diethyl oxalate 1∶1.5;（2） amination reaction by mechanochemically grinding with NH4OAc;（3） reduction reaction by Pd/C catalyzed hydrogenation in autoclave at 90 ℃ under 5 MPa pressure to afford the target product.Under the optimal conditions,the overall yield of homophenylalanine is 87%.The target compound and key intermediate were characterized by nuclear magnetic resonance（NMR）.The advantages of the above synthetic process are cheap raw materials,high overall yield and green procedure.

关 键 词：高苯丙氨酸 苯乙酮 机械研磨 草酸二乙酯 

分 类 号：TQ217[化学工程—有机化工]