四种左旋多巴和卡比多巴二肽的合成  

Synthesis of four dipeptide derivatives of levodopa and carbidopa

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作  者:谢树英 李如雯 刘中强 XIE Shu-ying;LI Ru-wen;LIU Zhong-qiang(School of Pharmacy,Hainan University,Haikou 570100,China)

机构地区:[1]海南大学药学院,海南海口570100

出  处:《化学研究与应用》2024年第3期593-599,共7页Chemical Research and Application

基  金:国家自然科学基金项目(22167012)资助。

摘  要:左旋多巴(L-DOPA)是目前治疗帕金森病最有效的药物,被称作“黄金标准”;卡比多巴(Carbidopa)是外周芳香族氨基酸脱羧酶(DDC)抑制剂,与L-DOPA合用,可使L-DOPA的疗效增强。目前文献记载的含多巴二肽衍生物合成方法条件复杂、步骤繁琐、消耗大量试剂、成本高且产率低。本课题采用N-和C-端无保护的左旋多巴和氨基酸琥珀酰亚胺酯为原料,通过两步法合成了四种左旋多巴二肽衍生物;该方法简单、经济、目标产物产率高。采用上述合成策略,成功合成了四种全新的卡比多巴二肽衍生物。即H-Met-Carbidopa-OH、H-Val-Carbidopa-OH、H-Ala-Carbidopa-OH、H-Phe-Carbidopa-OH。采用HR-MS、^(1)H-NMR、^(13)C-NMR对化合物进行结构表征。溶解度测试表明,在pH为6.1~6.5之间,四种L-DOPA二肽与四种Carbidopa二肽的水溶性皆大于0.050 mol·L^(-1),较L-DOPA与Carbidopa的水溶性都有显著的提升。L-DOPA is the most effective drug for treating Parkinson's disease at present,which is called " gold standard";Carbidopa is a peripheral activity inhibitor of aromatic amino acid decarboxylase(DDC),which can enhance the efficacy of L-DOPA when combined with L-DOPA.At present,the synthesis methods of dopa dipeptide derivatives described in the literature are complicated,complicated,consuming a lot of reagents,high cost and low yield.In this paper,four kinds of levodopa dipeptide derivatives were synthesized by two steps using N-and C-terminal unprotected levodopa and amino acid succinimide as raw materials.The method is simple,economical and had high yield of target product.Four new carbidopa dipeptide derivatives were synthesized successfully by using the above synthetic strategies.They were H-Met-Carbidopa-OH,H-Val-Carbidopa-OH,H-Ala-Carbidopa-OH,H-Phe-Carbidopa-OH.The products were identified by HR-MS,~1H-NMR and ^(13)C-NMR.The solubility tests showed that the water solubility of four L-DOPA dipeptides and four Carbidopa dipeptides was greater than 0.050 mol·L^(-1) at pH 6.1~6.5,which was significantly higher than the water solubility of L-DOPA and carbidopa.

关 键 词:左旋多巴 卡比多巴 二肽 合成 溶解度 

分 类 号:O625[理学—有机化学]

 

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