3-(3′-羟基)丁基苯酞氨基酸酯衍生物的设计与合成

Design and Synthesis of Amino-Acid Esters of 3-(3′-hydroxy)butylphthalide

3-(3′-羟基)丁基苯酞是丁苯酞在体内的代谢产物,具有多种药理作用,可以作为一种新的活性成分应用于药物开发中。本文以甘氨酸、甲硫氨酸和亮氨酸为起始原料,经过Boc保护,再与3-(3′-羟基)丁基苯酞进行缩合,脱保护3步反应合成了3-(3′-羟基)丁基苯酞的氨基酸酯。以期提高水溶性和改善药代动力学性质,获得3-(3′-羟基)丁基苯酞的前药。

3-（3＇-hydroxy）butylphthalide is one of the metabolic product of butylphthalide, for its diverse pharmacological activities. 3-（3＇-hydroxy）butylphthalide can be applied to drug development as a new kind of active ingredient. In this paper, the amino-acid esters of 3-（3＇-hydroxy）butylphthalide have been syn- thesized by three step reactions starting from glycine, methionine and leueine through （Boe）20 protect, condensation and deprotection. It was expected that the amino-acid esters of 3-（3＇-hydroxy）butylphthalide can improve water-solubility and pharmacokinetic parameters as prodrugs of butylphthalide.