Synthesis and antiviral evaluation of 2',2',3',3'-tetrafluoro nucleoside analogs.
Herein, we report the synthesis of novel 2',2',3',3'-tetrafluorinated nucleoside analogs along with their phosphoramidate prodrugs. A tetrafluoro ribose moiety was coupled with different Boc/benzoyl-protected nucleobases under Mitsunobu conditions. After deprotection, tetrafluorinated nucleosides13b,14b,20b-22bwere reacted with phenyl-(isopropoxy-L-alaninyl)-phosphorochloridate to afford corresponding monophosphate prodrugs24b-28b. All synthesized compounds were evaluated against several DNA and RNA viruses including HIV, HBV, HCV, Ebola and Zika viruses.
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ozkan
O
Sari
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Leda
L
Bassit
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Christina
C
Gavegnano
Cocrystal Pharma, Inc., 1860 Montreal Road, Tucker, GA 30084, USA.
Tamara R
TR
McBrayer
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Louise
L
McCormick
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Bryan
B
Cox
Cocrystal Pharma, Inc., 1860 Montreal Road, Tucker, GA 30084, USA.
Steven J
SJ
Coats
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Franck
F
Amblard
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Raymond F
RF
Schinazi
Antiviral; Fluorine; Mitsunobu; Nucleoside; Prodrug