恩他卡朋的合成

Synthesis of Entacapone

恩他卡朋是一种特异性外周儿茶酚胺-O-甲基转移酶抑制剂,用于帕金森病的辅助治疗。恩他卡朋的合成路线是以香兰素为原料,经硝化,脱甲基得到中间体3,4-二羟基-5-硝基苯甲醛;而另一中间体N,N-二乙基氰乙酰胺由氯乙酰氯经胺化,氰化得到。3,4-二羟基-5-硝基苯甲醛和N,N-二乙基氰乙酰胺经Knoevengal缩合反应和重结晶纯化得到产品,工艺总收率为31%。此路线操作简单,所用试剂廉价,产率高,适合工业化生产。

Entacapone is a potent and specific peripheral catechol-O-methyl-transferase (COMT) inhibitor and widely used in the treatment of Parkinson’s disease.Entacapone was synthesized and recrystallized from Knoevenagel condensation of the intermediates 3,4-dihydroxy-5-nitrobenzaldehyde and N,N-diethylcyanoacetamide.The first intermediate was obtained from the nitration and demethylation of vanillin,and the other one was offered by the amination and cyanation reaction of chloroacetyl chloride.The overall yield of the process is 31% (based on vanillin).This process using commercial available reagents was suitable for industrial production in high yield and under mild conditions.