1238305-24-2Relevant articles and documents
Stereoisomers of oseltamivir-synthesis, in silico prediction and biological evaluation
Hajzer, Viktória,Fi?era, Roman,Latika, Attila,Durmis, Július,Kollár, Jakub,Frecer, Vladimír,Tu?eková, Zuzana,Miertu?, Stanislav,Kostolansky, Franti?ek,Vare?ková, Eva,?ebesta, Radovan
, p. 1828 - 1841 (2017)
Oseltamivir is an important antiviral drug, which possess three chirality centers in its structure. From eight possible stereoisomers, only two have been synthesized and evaluated so far. We describe herein the stereoselective synthesis, computational activity prediction and biological testing of another three diastereoisomers of oseltamivir. These isomers have been synthesized using stereoselective organocatalytic Michael addition, cyclization and reduction. Their binding to viral neuraminidase N1 of influenza A virus was evaluated by quantum-chemical calculations and their anti-influenza activities were tested by an in vitro virus-inhibition assay. All three isomers displayed antiviral activity lower than that of oseltamivir, however, one of the stereoisomers, (3S,4R,5S)-isomer, of oseltamivir showed in vitro potency towards the Tamiflu-sensitive influenza viral strain A/Perth/265/2009(H5N1) comparable to Tamiflu.
Thiol-free synthesis of oseltamivir and its analogues via organocatalytic michael additions of oxyacetaldehydes to 2-acylaminonitroalkenes
Rehak, Juraj,Huka, Martin,Latika, Attila,Brath, Henrich,Almassy, Ambroz,Hajzer, Viktoria,Durmis, Julius,Toma, Stefan,Sebesta, Radovan
experimental part, p. 2424 - 2430 (2012/09/07)
The organocatalytic addition of substituted oxyacetaldehydes to 2-acylaminonitroethenes proceeded with good to high diastereoselectivities and enantioselectivities. The resulting adducts reacted with ethyl 2-(diethoxyphosphoryl) acrylate to afford highly functionalized cyclohexenes. A thiol-free protocol for cyclization has been developed that leads to a separable mixture of two diastereoisomers. The unwanted diastereoisomer can be efficiently epimerized. The resulting cyclohexenes are precursors to oseltamivir and its analogues. The synthesis of the key reagent, 3-pentyloxyaldehyde, was also improved. Georg Thieme Verlag Stuttgart · New York.
Organocatalytic michael addition of aldehydes to protected 2-amino-1-nitroethenes: The practical syntheses of oseltamivir (tamiflu) and substituted 3-aminopyrrolidines
Zhu, Shaolin,Yu, Shouyun,Wang, You,Ma, Dawei
supporting information; experimental part, p. 4656 - 4660 (2010/08/20)
Figure Presented Hey Mickey, you're so fine! Organocatalytic Michael additions of aldehydes with protected 2-amino-1-nitroethene could go through three different transition-states to afford adducts with usual and unusual stereochemistry, thereby providing a facile entry to Tamiflu (see scheme) and substituted 3-aminopyrrolidines. TMS = trimethylsilyl, Ac = acetyl.
