Oseltamivir, synthesis

Oseltamivir synthesis from shikimic acid M. Federspiel and group. Organic Process Research Development 1999, 3, 266-274. Corey... 

Ma and coworkers have also developed an organocatalytic strategy for oseltamivir synthesis. They used 2-acetamidonitroethane as the Michael acceptor to circumvent the Curtius rearrangement in the later stages of the synthesis. Based on this approach, others later improved various aspects of the oseltamivir synthesis. ... 

A modification of Hayashi s (—)-oseltamivir synthesis was recently reported by Ma et al. [64]. The group was able to replace the Michael acceptor ( )-tert-butyl 3-nitroacrylate (156) with acetyl-protected 2-amino-l-nitroethene, thereby eliminating the three-step conversion of the ester to the acetylamino group required thus far. 

A step in the synthesis of the antiviral drug (-)-oseltamivir (Tamiflu) was the conversion of an amide to an imide with RuO /aq. NaCIO VCH Cl [74],... 

In May 2006, E. J. Corey at Harvard University and two of his co-workers published a short enantioselective pathway for the synthesis of oseltamivir. Corey came up with the idea after reading a New York Times article on the shortage of Tamiflu supply, after... 

Scheme 7.9. Synthesis of oseltamivir phosphate (1) employing an enzymatic monohydrolysis desymmetrization.

A. Oseltamivir inhibits neuraminidase, an enzyme that cleaves neuraminic acid from oligosaccharides. Neuraminidase activity aids the movement of viral particles through neuraminic acid-rich respiratory secretions and is required for the release of progeny virions. Inhibition of viral DNA polymerase is the mechanism of action of nucleoside analogue antiviral drugs. Interferons do stimulate the JAK-STAT signaling pathway but do not stimulate proliferation of immune cells. Ribavirin inhibits GTP synthesis, and the antiretroviral protease inhibitors (e.g., ritonavir) inhibit HIV protease. 

Y. Y. Yeung, S. Hong, and E. J. Corey, A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid, J. Am. Chem. Soc., 128 (2006) 6310-6311. 

S. Abrecht, P. Harrington, H. Iding, M. Karpf, R. Trussardi, B. Wirz, and U. Zutter, The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu) A challenge for synthesis process research, Chimia, 58 (2004) 621-929. 

Sullivan B, Carrera I et al (2009) Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (tamiflu) from ethyl benzoate. Angew Chem Int Ed 48 4229 1231... 

Karpf, M. et al. New, Azide-Free Transformation of Epoxides into 1,2-Diamino Compounds Synthesis of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu). 3.4.4 2001 [135]... 

An example of process optimization by metabolic engineering is the production of intermediates for the synthesis of oseltamivir. This neuraminidase inhibitory drug (Tamiflu ) acts against the common as well as the threatening asian flu. Quinic and shikimic acid can serve as precursors (Scheme 4.20A), but the shiki-... 

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