Synthesis of 5,5-difluoro-5-phosphono-pent-2-en-1-yl nucleosides as potential antiviral agents

Abstract

A series of hitherto unknown acyclic 5,5-difluoro-5-phosphono-pent-2-en-1-yl-pyrimidines, -purines and -(1,2,4)-triazolo-3-carboxamide were successfully synthesized from (E)-1-bromo-5-diethoxyphosphoryl-5,5-difluoro-pent-2-ene in a stereoselective manner.

Conformationally Locked Carbocyclic Nucleosides Built on a 4′-Hydroxymethyl-3′-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity

“…Recently, other non-CNAs have been described with important antiviral activity toward the closely related coxsackie B3 virus. , In one of these works, the use of 1,2,3-triazole-based non-natural nucleobases proved to be effective to improve the antiviral activity . However, in other cases, the use of non-natural nucleobases in linear CNAs has not led to significant antiviral activity against coxsackie B4 virus. , Despite all these precedents, at present, there is no approved specific treatment for coxsackie virus infections. The preliminary in vitro antiviral activity of the novel synthesized carbocyclic nucleoside 3d opens the door to carry out additional studies of structure–activity relationships as well as studies of the mode of action.…”

“… 54 However, in other cases, the use of non-natural nucleobases in linear CNAs has not led to significant antiviral activity against coxsackie B4 virus. 55 , 56 Despite all these precedents, at present, there is no approved specific treatment for coxsackie virus infections. The preliminary in vitro antiviral activity of the novel synthesized carbocyclic nucleoside 3d opens the door to carry out additional studies of structure–activity relationships as well as studies of the mode of action.…”