A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from d-glucose. Issue 16 (22nd April 2015)

• Record Type: Journal Article
• Authors: Kongkathip, Boonsong; Akkarasamiyo, Sunisa; Kongkathip, Ngampong
• Is Part Of: Tetrahedron. Volume 71:Issue 16(2015)
• Page Start: 2393
• Page End: 2399
• Publication Date: 2015-04-22
• Subjects: Oseltamivir phosphate -- Tamiflu -- Anti-influenza -- d-Glucose -- Bernet-Vasellar reaction -- Ring closing metathesis; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.02.081
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The anti -influenza drug, oseltamivir phosphate (Tamiflu) was synthesized fromd -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 fromd -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 SN 2 substitution of azide to give the same azido product, which then converted into oseltamivir phosphate. Graphical abstract: