D-脯氨酸催化的(3S,4S)-4-氨基-3-羟基-5-苯基戊酸衍生物的合成  

Synthesis of (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic Acid Derivatives Catalyzed by D-proline

作　　者：包可婷[1,2] 张伟[2] 李英霞[2] 胡春[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]复旦大学药学院,上海201203

出　　处：《合成化学》2016年第4期355-358,共4页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81573340);复旦大学卓学人才计划资助项目

摘　　要：报道了一条合成（3S,4S）-4-氨基-3-羟基-5-苯基戊酸（Ahppa）衍生物的新路线。以氨基保护的L-苯丙氨酸为起始原料,依次经Weinreb胺缩合、还原、aldol缩合及溴仿4步反应合成了3个Ahppa衍生物,总收率5.8%-6.7%,其结构经^1H NMR,^13C NMR和ESI-MS确证。对反应条件进行了探讨,结果表明：催化剂D-脯氨酸用量对反应收率影响不大,对立体选择性影响较大;氨基上保护基体积较大有利于提高反应立体选择性。A new route for the synthesis of （3S ,4S）-4-amino-3-hydroxy-5-phenylpentanoic acid derivatives was reported. The target compounds with overall yields of 5.8% - 6.7% were synthesized by condensation with Weinreb amide, reduction, aldol condensation reaction and bromine imitation reaction, using amino-protected L-phenylalanine as starting material. The structures were confirmed by ^1H NMR, ^13C NMR and ESI-MS. The exploration of reaction conditions showed that the loading amount of D-proline had no evident effect on the yield, but on stereoselectivity. Larger size protecting groups in substrate can enhanced the stereo-selectivity.

关 键 词：苯丙氨酸 天冬氨酸蛋白酶抑制剂 (3S 4S)-4-氨基-3-羟基-5-苯基戊酸 D-脯氨酸 催化 药物合成 

分 类 号：O623.736[理学—有机化学] R914.5[理学—化学]