Synthesis and Conformation of Novel 4'-Fluorinated 5'-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

Abstract

Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to 100 µM.

Copper-Catalyzed Defluorinative Borylation and Silylation of gem-Difluoroallyl Groups

“…Because the hydrolytic stability and lipophilicity of ( Z )-fluoroalkenes are higher than those of amides, they serve as bioisosteres for peptide bonds in protease-resistant peptidomimetics . In addition to these properties that are valuable for drug design, fluoroalkenes serve as synthetic intermediates to secondary and tertiary alkyl fluorides via hydrogenations, − sigmatropic rearrangements, , allylic substitutions, , nucleophilic allylations, Sigman–Heck reactions, and cycloadditions. , …”