An efficient triphosphate synthesis of a novel broad-spectrum antiviral nucleoside BCX4430

Abstract

Nucleoside analogs comprise the largest class of small-molecule drugs available for treating viral infections. These drugs are generally delivered as the parent 5ʹ-hydroxyl derivatives or as the corresponding ester prodrugs (5ʹ-monophosphate esters or various alkanoate esters) that must be converted to their triphosphate form to interact with viral polymerases and function as antiviral agents. BCX4430 (Galidesivir) is a broad-spectrum adenosine nucleoside analog that targets the RNA-dependent RNA polymerases (RdRps) of RNA virus. As the distorted ring structure of the azasugar present in BCX4430 precludes the application of standard chemical approaches for generating the triphosphate, we report a novel method for synthesizing the first azasugar triphosphate, which is an important reference material for the BCX4430 inhibitor.