- Stereoisomers of oseltamivir-synthesis, in silico prediction and biological evaluation
-
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.
- 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
-
-
Read Online
- Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions
-
The thiourea-catalyzed asymmetric synthesis of highly enantioenriched spirocyclopentaneoxindoles containing chiral amide functional groups using simple 3-substituted oxindoles and nitrovinylacetamide as starting materials was achieved successfully. This protocol features operational simplicity, high atom economy, and high catalytic asymmetry, thus representing a versatile approach to the synthesis of highly enantioenriched spirocyclopentaneoxindoles.
- Du, Yonglei,Li, Jian,Chen, Kerong,Wu, Chenglin,Zhou, Yu,Liu, Hong
-
supporting information
p. 1342 - 1349
(2017/07/18)
-
- Thiol-free synthesis of oseltamivir and its analogues via organocatalytic michael additions of oxyacetaldehydes to 2-acylaminonitroalkenes
-
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.
- 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)
-
- Process for the preparation of 1-nitro-4-oxobutanylamides
-
It is disclosed a process for the preparation of 1-nitro-4-oxobutanylamides of general formula Ia and Ib or opposite enantiomers thereof, wherein R1 is H, alyl, alkyloxycarbonyl, arylalkyloxycarbonyl with a number of carbon atoms up to 24, or the same as
- -
-
Page/Page column 14
(2011/11/13)
-
- Organocatalytic michael addition of aldehydes to protected 2-amino-1-nitroethenes: The practical syntheses of oseltamivir (tamiflu) and substituted 3-aminopyrrolidines
-
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.
- Zhu, Shaolin,Yu, Shouyun,Wang, You,Ma, Dawei
-
supporting information; experimental part
p. 4656 - 4660
(2010/08/20)
-