(S)-4-苄氧基取代苯丙胺醇衍生物的制备  

Synthesis of(S)-4-Benzyloxy-substituted Amphetamine Alcohol Derivatives

作　　者：陈耀 王晓奎[2] 李松[2] 胡春[3] Chen Yao;Wang Xiaokui;Li Song;Hu Chun(Yulin Campus,Guangxi Medical University,Guangxi,Yulin 537000;Beijing Institute of Pharmacology and Toxicology,Beijing 100850;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]广西医科大学玉林校区,广西玉林537000 [2]军事医学科学院毒物药物研究所,北京100850 [3]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《广东化工》2023年第9期67-69,共3页Guangdong Chemical Industry

摘　　要：采用以L-N-Boc酪氨酸甲酯为原料,经苄基保护4位酚羟基、LiAlH4还原甲酯、脱苄基保护、醚化反应、脱Boc保护基等反应,合成了中间体3和(S)-4-苄氧基取代苯丙胺醇衍生物3个。实验过程中得到的中间体3和(S)-4-苄氧基取代苯丙胺醇衍生物分别为(S)-3-(4-羟基苯基)-2-叔丁氧甲酰氨基-1-丙醇、(S)-3-(4-苄氧苯基)-2-氨基-1-丙醇、(S)-3-[4-(3,4-二氟苄氧苯基)]-2-氨基-1-丙醇和(S)-3-[4-(2,6-二氟苄氧苯基)]-2-氨基-1-丙醇,所得化合物的化学结构经质谱和核磁共振氢谱确证。本合成路线具有操作简单、收率高的特点,其中中间体3可用于氨基醇类衍生物的合成,而(S)-4-苄氧基取代苯丙胺醇衍生物的合成提供了基础化合物和合成方法参考,以发现和研制新的活性药物。A key intermediate 3 and(S)-4-benzyloxy-substituted amphetamine alcohol derivative were synthesized from L-Boc tyrosine methyl ester through key reaction steps such as benzyl protection of phenolic hydroxyl,reduction of LiAlH4,deprotection,substituted benzylation and Boc removal.The key intermediates and S-phenylpropanolamine derivatives obtained in the experiment were tert-butyl(S)-(1-hydroxy-3-(4-hydroxyphenyl)propan-2-yl)carbamate,(S)-2-amino-3-(4-(benzyloxy)phenyl)propan-1-ol,(S)-2-amino-3-(4-(2,6-difluorobenzyloxy)phenyl)propan-1-ol and(S)-2-amino-3-(4-(3,4-difluorobenzyloxy)phenyl)propan-1-ol respectively,and the chemical structures of the obtained compounds were confirmed by mass spectrum and 1H NMR.This synthetic route has the characteristics of simple operation and acceptable yield.This key intermediate 3 can be used for the synthesis of amino alcohol derivatives.The synthesis of S-phenyl propanolamine derivatives provides basic materials and synthetic methods for finding and developing new active drugs.

关 键 词：L-N-Boc酪氨酸甲酯 (S)-4-苄氧基取代苯丙胺醇衍生物 LiAlH4还原 醚化反应 合成 

分 类 号：TQ460.1[化学工程—制药化工]