Synthesis 2013; 45(3): 389-395
DOI: 10.1055/s-0032-1317948
paper
© Georg Thieme Verlag Stuttgart · New York

Formal Synthesis of (–)-Oseltamivir Phosphate

Milos Trajkovic
Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia   Fax: +381(11)3282537   Email: rsaicic@chem.bg.ac.rs
,
Zorana Ferjancic*
Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia   Fax: +381(11)3282537   Email: rsaicic@chem.bg.ac.rs
,
Radomir N. Saicic*
Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia   Fax: +381(11)3282537   Email: rsaicic@chem.bg.ac.rs
› Author Affiliations
Further Information

Publication History

Received: 01 November 2012

Accepted after revision: 05 December 2012

Publication Date:
20 December 2012 (online)


Abstract

The formal synthesis of (–)-oseltamivir phosphate (Tamiflu tm ) was accomplished starting from (S)-pyroglutamic acid. The synthesis comprised two carbon–carbon bond forming reactions, the first one being a diastereoselective, indium-mediated allylation of a pyroglutamic aldehyde derivative. However, attempts to effect the second carbon–carbon bond formation – cyclohexene ring closure – using an enol-exo aldolization of a dialdehyde resulted in the formation of a product with the opposite regioselectivity. This shortcoming could be overcome by using a reaction sequence of Mannich methylenation/ring-closing metathesis, which provided the desired regioisomer in high yield.

Supporting Information