Synthesis of T-705-Ribonucleoside and T-705-Ribonucleotide and Studies of Chemical Stability.
T-705 (favipiravir) is a fluorinated hydroxypyrazine carboxamide that exhibits antiviral activities against a variety of RNA viruses. Given the lack of potent agents to combat these infections caused by a large number of high-impact pathogens, significant emphasis has been put on studies of the antiviral properties of T-705 and its mechanism of action. T-705 acts as a nucleobase analogue; it is therefore metabolized to the corresponding ribonucleoside triphosphate intracellularly. Herein we report a reliable synthesis of T-705-ribonucleoside as well as its 5'-monophosphate. Moreover, we disclose detailed studies on the remarkable lability of the heterocycle when attached to ribose under very mild conditions, as typically applied in biochemical studies.
Organic Chemistry, Department of Chemistry, Faculty of Sciences, Hamburg University, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
Johanna
0000-0001-6368-3273
J
Huchting
Organic Chemistry, Department of Chemistry, Faculty of Sciences, Hamburg University, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
Matthias
M
Winkler
Organic Chemistry, Department of Chemistry, Faculty of Sciences, Hamburg University, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
Hiba
H
Nasser
Organic Chemistry, Department of Chemistry, Faculty of Sciences, Hamburg University, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
Chris
C
Meier
D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D012263:Ribonucleosides
T-705; antiviral agents; favipiravir; nucleosides; pyrazine ribonucleosides