磷酸奥司米韦的合成研究

目的 研究磷酸奥司米韦的合成方法。方法 以莽草酸为起始原料，通过酯化、缩酮保护、甲磺酰化、缩酮交换、还原，闭环反应得关键中间体(3R,4S,5S)-4,5-环氧基-3-(1-乙基丙氧基)-1-环己烯甲酸乙酯(2)；化合物2在氯化镁催化下和叔丁胺反应，经甲磺酰化、闭环得氮丙啶中间体，再经开环、乙酰化、脱叔丁基、脱烯丙基后成磷酸盐共13步反应得抗病毒药磷酸奥司米韦。结果与结论 合成的磷酸奥司米韦经1H-NMR和MS谱确证结构，总收率为29.5 %。

Synthesis of oseltamivir phosphate

Aim To investigate an improved synthetic process of oseltamivir phosphate, an antiviral drug. Methods Starting from (–)-shikimic acid, the key epoxide (2) was synthesized via esterification, ketalization, mesylation, transketalization, reduction and intramolecular SN2 reaction. 2 was treated with tert-butylamine for epoxide-opening in the presence of MgCl2, and then brought into mesylation and intramolecular SN2 reaction to form the aziridine 10. After MsOH-promoted opening of the aziridine with diallylamine, followed by acetylation and successive removal of tert-Butyl and allyl group, oseltamivir was eventually obtained. Results and conclusions Oseltamivir phosphate was synthesized via a 13-step sequence in a total yield of 29.5 % and its structure was identified by 1H-NMR and MS.