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Synthesis 2013; 45(3): 389-395
DOI: 10.1055/s-0032-1317948
DOI: 10.1055/s-0032-1317948
paper
Formal Synthesis of (–)-Oseltamivir Phosphate
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
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
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For review articles on the development of the industrial synthesis, see:
For improvements and more detailed accounts on industrial synthesis, see:
For other semi-syntheses from shikimic acid, see:
Synthesis of racemic Tamiflu tm :
For review articles on synthetic strategies to oseltamivir, see: