A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from D-glucose

作者：Kongkathip Boonsong; Akkarasamiyo Sunisa; Kongkathip Ngampong^*

来源：Tetrahedron, 2015, 71(16): 2393-2399.

DOI：10.1016/j.tet.2015.02.081

• Oseltamivir phosphate
• Tamiflu
• Anti-influenza
• D-Glucose
• Bernet-Vasellar reaction
• Ring closing metathesis

The anti-influenza drug, oseltamivir phosphate (Tamiflu) was synthesized from a-glucose via a novel and efficient synthetic route. A unique feature of the synthesis is that the key intermediate aziridine cyclohexene was synthesized as a mixture of diastereomers, via a metal-mediated domino reaction and ring closing metathesis (RCM). The iodoxylose compound was prepared in 9 steps from D-glucose. Both isomers of aziridine cyclohexene intermediate could be converted into Tamiflu via two pathways. First, both isomers of aziridine cyclohexene underwent aziridine-ring opening yielded diastereomeric of 1,2-amino mesylate cyclohexene esters. The trans-1,2-amino mesylate isomer could be transformed to tamiflu by formation of aziridine then regio- and stereoselective nucleophilic substitution of the azide to afford 1,2-amino azido compound whereas the cis-isomer could be transformed directly by S(N)2 substitution of azide to give the same azido product, which then converted into oseltamivir phosphate.

• 出版日期2015-4-22