磷酸二酯酶5抑制剂他达拉非及其中间体的合成研究  

Synthesis of phosphodiesterase 5 inhibitor tadalafil and its intermediates

作　　者：张彬 李新志 孔祥雨 蔡文卿 段崇刚 刘文涛 ZHANG Bin;LI Xin-zhi;KONG Xiang-yu;CAI Wen-qing;DUAN Chong-gang;LIU Wen-tao(Shandong Provincial Key Laboratory of Chemical Drugs,Shandong Academy of Pharmaceutical Science,Jinan 250101,China)

机构地区：[1]山东省药学科学院山东省化学药物重点实验室,山东济南250101

出　　处：《中国药物化学杂志》2022年第11期843-848,共6页Chinese Journal of Medicinal Chemistry

基　　金：济南市创新团队项目(2021GXRC069)。

摘　　要：目的 合成他达拉非,并对其合成工艺进行优化改进。方法 以D-色氨酸甲酯盐酸盐为起始原料,依次通过与胡椒醛发生P-S反应,N-酰化反应和环合反应合成他达拉非。结果与结论合成反应总收率87.1%,纯度99.5%。所得产品经熔点、质谱和核磁共振氢谱等方法确证结构,改进后的工艺操作简单、成本较低、对环境更友好,有利于工业化生产。Aim to synthesize phosphodiesterase 5 inhibitor tadalafil,and optimize the synthesis process.Starting from D-tryptophan methyl ester hydrochloride,tadalafil was obtained by P-S condensation reaction with piperonal,N-acylation reaction with chloroacetyl chloride and cyclization reaction with methylamine ethanol.The yield of three reactions reached 87.1%,and final purity reached 99.5%.The final product was confirmed as tadalafil by melting point,MS and~1H-NMR methods.The optimized process has the advantages of simpler operation,lower cost,more environmentally friendly and more conducive to industrial production.

关 键 词：他达拉非 PDE5抑制剂 工艺优化 P-S反应 

分 类 号：R914.5[医药卫生—药物化学]