Short Chemoenzymatic Azide‐Free Synthesis of Oseltamivir (Tamiflu): Approaching the Potential for Process Efficiency

A short chemoenzymatic and azide-free synthesis of oseltamivir was attained with the key steps consisting of a one-pot Dauben-Michno oxidative transposition and amination and a reductive transposition of an acrylate.

[1]  Y. Hayashi,et al.  High-yielding synthesis of the anti-influenza neuramidase inhibitor (-)-oseltamivir by three "one-pot" operations. , 2009, Angewandte Chemie.

[2]  T. Fukuyama,et al.  A practical synthesis of (-)-oseltamivir. , 2007, Angewandte Chemie.

[3]  A. Willis,et al.  A chemoenzymatic synthesis of the anti-influenza agent Tamiflu , 2008 .

[4]  W G Laver,et al.  Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. , 1997, Journal of the American Chemical Society.

[5]  T. Hamada,et al.  Efficient short step synthesis of Corey's tamiflu intermediate. , 2008, Organic letters.

[6]  M. Kanai,et al.  De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3. , 2006, Journal of the American Chemical Society.

[7]  P. Collins,et al.  Galactose-conjugates of the oseltamivir pharmacophore--new tools for the characterization of influenza virus neuraminidases. , 2009, Organic & biomolecular chemistry.

[8]  W G Laver,et al.  Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors. , 1998, Journal of medicinal chemistry.

[9]  M. Kanai,et al.  Second generation catalytic asymmetric synthesis of Tamiflu: allylic substitution route. , 2007, Organic letters.

[10]  H. Iding,et al.  New, efficient synthesis of oseltamivir phosphate (Tamiflu) via enzymatic desymmetrization of a meso-1,3-cyclohexanedicarboxylic acid diester. , 2008, The Journal of organic chemistry.

[11]  W. G. Dauben,et al.  Direct oxidation of tertiary allylic alcohols. A simple and effective method for alkylative carbonyl transposition , 1977 .

[12]  D. Hagberg,et al.  An iron carbonyl approach to the influenza neuraminidase inhibitor oseltamivir. , 2007, Chemical communications.

[13]  An-Suei Yang,et al.  Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity. , 2007, Journal of the American Chemical Society.

[14]  Z. Yao,et al.  Ring-closing metathesis-based synthesis of (3R,4R,5S)-4-acetylamino-5-amino-3-hydroxy- cyclohex-1-ene-carboxylic acid ethyl ester: a functionalized cycloalkene skeleton of GS4104. , 2006, The Journal of organic chemistry.

[15]  M. Karpf,et al.  New, azide-free transformation of epoxides into 1,2-diamino compounds: synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu). , 2001, The Journal of organic chemistry.

[16]  T. Hudlický,et al.  Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (Tamiflu) from ethyl benzoate. , 2009, Angewandte Chemie.

[17]  Andrew G. Watts,et al.  Palladium-catalysed allylic amination for the direct synthesis of epi-4-alkylamino-N-acetylneuraminic acid derivatives , 2009 .

[18]  S. Abrecht,et al.  The synthetic-technical development of oseltamivir phosphate Tamiflu™ : A race against time , 2007 .

[19]  B. Trost,et al.  A concise synthesis of (-)-oseltamivir. , 2008, Angewandte Chemie.

[20]  John Andraos,et al.  Global Green Chemistry Metrics Analysis Algorithm and Spreadsheets: Evaluation of the Material Efficiency Performances of Synthesis Plans for Oseltamivir Phosphate (Tamiflu) as a Test Case , 2009 .

[21]  D. Gibson,et al.  Toluene degradation by Pseudomonas putida F1. Nucleotide sequence of the todC1C2BADE genes and their expression in Escherichia coli. , 1989, The Journal of biological chemistry.

[22]  Tomas Hudlicky,et al.  Investigation of steric and functionality limits in the enzymatic dihydroxylation of benzoate esters. Versatile intermediates for the synthesis of pseudo-sugars, amino cyclitols, and bicyclic ring systems. , 2009, Organic & biomolecular chemistry.

[23]  E. Corey,et al.  A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid. , 2006, Journal of the American Chemical Society.

[24]  T. Foderaro,et al.  Research and Development of a Second-Generation Process for Oseltamivir Phosphate, Prodrug for a Neuraminidase Inhibitor , 2004 .

[25]  M. Kanai,et al.  Synthetic Strategies for Oseltamivir Phosphate , 2008 .

[26]  T. Hudlický,et al.  Medium-Scale Preparation of Useful Metabolites of Aromatic Compounds via Whole-Cell Fermentation with Recombinant Organisms , 2002 .

[27]  Vittorio Farina,et al.  Tamiflu: Das Versorgungsproblem , 2006 .

[28]  P. Wender,et al.  A general methodology for pseudoguaiane synthesis: total synthesis of (.+-.)-damsinic acid and (.+-.)-confertin , 1979 .

[29]  M. Hennig,et al.  Industrial Synthesis of the Key Precursor in the Synthesis of the Anti-Influenza Drug Oseltamivir Phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate , 1999 .

[30]  M. Kanai,et al.  A synthesis of Tamiflu by using a barium-catalyzed asymmetric Diels-Alder-type reaction. , 2009, Angewandte Chemie.

[31]  M. Kanai,et al.  An alternative synthesis of Tamiflu®: a synthetic challenge and the identification of a ruthenium-catalyzed dihydroxylation route , 2009 .

[32]  V. Farina,et al.  Tamiflu: the supply problem. , 2006, Angewandte Chemie.

[33]  Chi‐Huey Wong,et al.  A concise and flexible synthesis of the potent anti-influenza agents tamiflu and tamiphosphor. , 2008, Angewandte Chemie.

[34]  J. Magano Synthetic approaches to the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir phosphate (Tamiflu) for the treatment of influenza. , 2009, Chemical reviews.

[35]  K. Kent,et al.  Practical Total Synthesis of the Anti-Influenza Drug GS-4104 , 1998 .

[36]  M. Kanai,et al.  A concise synthesis of Tamiflu: third generation route via the Diels–Alder reaction and the Curtius rearrangement , 2007 .