A novel azide-free asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from Roche's epoxide

作者：Nie, Liang-Deng; Wang, Fei-Feng; Ding, Wei; Shi, Xiao-Xin^*; Lu, Xia

来源：Tetrahedron: Asymmetry , 2013, 24(11): 638-642.

DOI：10.1016/j.tetasy.2013.04.016

• NEURAMINIDASE INHIBITOR OSELTAMIVIR
• POTENT ANTIINFLUENZA ACTIVITY
• RING-CLOSING METATHESIS
• HIGH-YIELDING SYNTHESIS
• ACID ETHYL-ESTER
• SHIKIMIC ACID
• (-)-SHIKIMIC ACID
• CHEMOENZYMATIC SYNTHESIS
• EFFICIENT SYNTHESIS
• CONCISE SYNTHESIS

A novel azide-free asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu (R)) starting from Roche's epoxide is described. Roche epoxide 2 was converted into N-acetyl aminoalcohol 3 in 95% yield via a BF3 center dot OEt2-catalyzed epoxide-opening with acetonitrile as a nucleophile. Compound 3 was then transformed into a methanesulfonate 4 in 98% yield. Compound 4 was converted into aziridine 5 in 91% yield. Aziridine 5 was subsequently converted into oseltamivir phosphate 1 via two paths (a and b). In the path a, compound 5 underwent aziridine-opening with diallylamine as a nucleophile to afford compound 7 in 93% yield; compound 7 could then be converted into oseltamivir phosphate 1 in 88% yield. In path b, compound 5 underwent aziridine-opening with isopropyl 2,2,2-trichloroacetimidate as a nucleophile to afford compound 8 in 94% yield, which was then converted into oseltamivir phosphate 1 in 82% yield.

• 出版日期2013-6-15
• 单位华东理工大学