Stereoselective Synthesis of Nucleotide Analog Prodrugs (ProTides) via an Oxazaphospholidine Method.

ABSTRACT: This paper describes the stereocontrolled synthesis of O-aryl phosphoramidate nucleotide prodrugs (ProTides), namely Remdesivir, Sofosbuvir, and NUC-1031, using an oxazaphospholidine method. The 5'-phosphoramidate derivatives were synthesized via a one-pot process involving the condensation of nucleoside 5'-oxazaphospholidine derivatives with phenol, bromination of the resulting phosphite using N-bromosuccinimide, and subsequent reaction with an amine. The target compounds were obtained with high stereoselectivity (dr >99:1). This one-pot strategy substantially reduced the reaction time from those of traditional phosphorylation methods using P(V) derivatives, providing an efficient and streamlined route to ProTides.

SUBMITTER: Nakamura M 

PROVIDER: S-EPMC12090215 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature