Formal Synthesis of (–)-Oseltamivir Phosphate

Milos Trajkovic; Zorana Ferjancic; Radomir N. Saicic

doi:10.1055/s-0032-1317948

Synthesis, Table of Contents

Synthesis 2013; 45(3): 389-395
DOI: 10.1055/s-0032-1317948

paper

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

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Abstract

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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.

Key words

antiviral agents - allylation - cyclization - metathesis - total synthesis

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References

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