磷酸奥司米韦的合成

Synthesis of Oseltamivir Phosphate

(–)-莽草酸经酯化、丙酮保护、甲磺酰化、缩酮交换、还原开环和闭环反应得中间体环氧化物,之后经叠氮开环氧、Staudinger反应合成氮丙啶中间体,然后再用叠氮开氮丙啶环、氨基乙酰化、还原叠氮基后与磷酸成盐得到抗流感病毒药磷酸奥司米韦。重点优化了丙酮保护、氮丙啶形成和叠氮还原3个步骤。避免了使用价格较贵的试剂,以及严格无水且易燃易爆的苛刻反应条件,总收率约为14%。

Starting from （-）-shikimic acid, oseltamivir phosphate was synthesized via twelve steps with an overall yield of about 14 %. Improvement was achieved in the ketalization, aziridine formatiom and azide reduction steps, avoiding the absolute anhydrous or potentially explosive conditions in the process.