阿加曲班的合成

Synthesis of Argatroban

(2R,4R)-4-甲基哌啶-2-甲酸通过酯化后,与(S)-2-[(叔丁氧羰基)氨基]-5-(3-硝基胍基)戊酸缩合,去Boc保护基,与3-甲基-8-喹啉磺酰氯缩合,再经酯水解、Pd/C氢化还原喹啉环及脱硝基保护、精制得抗血栓药物阿加曲班,总收率约12%,纯度99.5%。该合成方法操作简单,工艺稳定,适合工业化生产。

Argatroban, an antithrombotic drug, was synthesized from （2R,4R）-4-methylpiperidine-2-carboxylic acid via esterification, condensation with （S） -2- E （tert-butoxycarbonyl） amino] -5- （3-nitroguanidino） pentanoic acid, deprotection of Boc group, condensation with 3-methylquinoline-8-sulfonyl chloride, hydrolysis, Pd/C-catalyzed hydrogenation and simultaneous deprotection, and purification with an overall yield about 12% and a purity of 99.5%. This method was suitable for industrialization because of its simple operation and stable process.