Hajzer V.,SYNKOLA Ltd. |
Fisera R.,SYNKOLA Ltd. |
Latika A.,SYNKOLA Ltd. |
Durmis J.,SYNKOLA Ltd. |
And 8 more authors.
Organic and Biomolecular Chemistry | Year: 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. © The Royal Society of Chemistry.
Crowley P.J.,Hill International |
Lamberth C.,Syngenta |
Muller U.,Syngenta |
Wendeborn S.,Syngenta |
And 3 more authors.
Tetrahedron Letters | Year: 2010
Novel trisubstituted pyrido[3,2-e][1,2,4]triazines have been found to possess similar biological activity to the corresponding pyridopyrazine fungicides against important phytopathogens such as Mycosphaerella graminicola (wheat leaf blotch), Magnaporthe grisea (rice blast), and Rhizoctonia solani (rice sheath blight). They have been prepared for the first time from a monocyclic triazine by Niementowski-type ring condensation. © 2010 Elsevier Ltd. All rights reserved.
Elucidation of Photoisomerization-Related Structural Changes in an Acrylamide-Bridged Binaphthalene-Diazene Macrocyclic Chiroptical Switch by Experimental Electronic Circular Dichroism Spectra Simulation: Role of Dispersion Corrections
Kerner L.,Comenius University |
Kickova A.,Comenius University |
Kickova A.,Synkola Ltd. |
Filo J.,Comenius University |
And 2 more authors.
Journal of Physical Chemistry A | Year: 2015
Nondestructive readout of light-driven molecular memory devices can be achieved by monitoring the alterations in the chiroptical properties of 1,1′-binaphthalene as a conformationally responsive chiral group. In our system, this signaling unit is connected via acrylamide linkers to the receiving diphenyldiazene fragment, which undergoes significant geometrical changes upon (E)/(Z)-photoisomerization. The compound functions as a stable photochromic switch by alternating irradiation at 365/465 nm, with fully reversible modulation of circular dichroism (CD) signal intensity (up to 1:3) and extended thermal stability of the (Z)-isomer. According to molecular modeling, the acrylamide spacers are due to the imposed cyclic strain upon photoisomerization forced to switch amide conformations, which is markedly reflected in the CD spectra, whereas binaphthalene conformational changes are mostly neglected both by theory and by experiment. In CD simulation by TD-DFT, CAM-B3LYP outperforms B3LYP and M06 by means of similarity analysis, whereas the last mentioned functional also delivers satisfactory performance qualitatively. The inclusion of dispersion corrections during geometry optimization was crucial to retain consistency with the measured spectra. By carefully considering all relevant conformations of this 20-membered macrocycle, reasonable agreement with the experiment is reached not only for the CD simulation of the individual conformers but also of the photoisomerization process of their admixture. © 2015 American Chemical Society.
Hajzer V.,Synkola Ltd. |
Alexy P.,Slovak University of Technology in Bratislava |
Latika A.,Synkola Ltd. |
Durmis J.,Synkola Ltd. |
Sebesta R.,Comenius University
Monatshefte fur Chemie | Year: 2015
Abstract Stereoselective Michael addition of 2-(pentan-3-yloxy)acetaldehyde to N-[(Z)-2-nitroethenyl]acetamide is a key step in the organocatalytic synthesis of oseltamivir, active ingredient in the anti-influenza drug Tamiflu. Several important reaction parameters were analyzed by the help of design of experiments and optimum reaction conditions were found. These conditions led to improvements of the reaction outcomes. © 2015 Springer-Verlag Wien.
Rehak J.,Synkola Ltd. |
Huka M.,Comenius University |
Latika A.,Synkola Ltd. |
Brath H.,Synkola Ltd. |
And 5 more authors.
Synthesis (Germany) | Year: 2012
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.