Synthesis of SATE Prodrug of 6'-Fluoro-6'-methyl-5'-noradenosine Nucleoside Phosphonic Acid as a New Class of Anti-HIV Agent

Abstract

A very simple synthetic route of a novel SATE prodrug type of 6'-fluoro-6'-methyl-5'-noradeonosine carbocyclic nucleoside phosphonic acid is described. The key fluorinated alcohol intermediate 7 was prepared from the epoxide intermediate 6a via selective ring-opening of epoxide. Coupling of 7 with N 6 -bis-Boc-adenine under a Mitsunobu reaction followed by phosphonation and deprotection afforded the carbocyclic phosphonic acid. The chemical stability of the bis(SATE) derivative 13 was measured at neutral (pH 7.2) and slightly acidic (Milli-Q water, pH 5.5) pH. The antiviral activity test of the SATE prodrug 13 and its parent nucleoside phosphonic acid 11 were evaluated against HIV-1.

Synthesis of Nucleoside Phosphate and Phosphonate Prodrugs

“…Li et al prepared the 6′-fluoro-6′-methyl-5′-noradenosine phosphonic acid bis­(SATE)-prodrug 133 by reaction of phosphonic acid 132 with S -(2-hydroxyethyl)-2,2-dimethylpropanethioate in the presence of MSNT (Scheme ).…”