Synthesis and Antiviral Activity Evaluation of 5',5'-Difluoro-2'-methylapiosyl Nucleoside Phosphonic Acid Analogs

Abstract

AbstractRacemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potentantiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfullyproceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection ofdiethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds againstvarious viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, andthymine) have weak anti-HIV or HCMV activity.Keywords: Antiviral Agents; 5',5'-Difluoro-2'-methyl-apiose Nucleoside Phosphonic Acid Analogues; VorbruggenReaction 1. Introduction The modification of the nucleosides and/or sugarmoiety of a natural nucleoside is an obvious choice fordeveloping new antiviral compounds, and apiose-basednucleoside could serve this purpose.Recently, apiose 5'-nor nucleoside phosphonate