Synthesis and Antiviral Evaluation of 3'‐ C ‐Hydroxymethyl‐3'‐ O ‐Phosphonomethyl‐β‐D‐5'‐deoxyxylose Nucleosides

L‐2'‐deoxythreose nucleoside phosphonates PMDTA and PMDTT possess potent anti‐HIV activity. Herein, a novel class of 3'‐ C ‐branched‐ l ‐threose nucleoside phosphonate analogs, 5'‐deoxy‐3'‐ C ‐hydroxymethyl‐3'‐ O ‐phosphonomethyl‐ d ‐xylose nucleosides, were synthesized and biologically evaluated. The key sugar intermediate 3‐ C ‐benzyloxymethyl‐3‐ O ‐diethylphosphonomethyl‐1,2‐ O ‐isopropylidene‐α‐ d ‐5‐deoxyxylose ( 8 ) was firstly synthesized, which may be an interesting scaffold for access to diverse 3'‐ C ‐branched l ‐threosyl nucleoside phosphonate derivatives. And the key synthesis involved Wittig olefination of 1,2‐ O ‐isopropylidene‐3‐oxo‐α‐ d ‐5‐deoxyxylose, stereoselective dihydroxylation of alkenes by aqueous KMnO 4 , selective benzylation of hydroxymethyl group under activation of dibutyltin oxide, and introduction of phosphonate group by nucleophilic substitution. Eventually, glycosylation under Vorbrüggen conditions provided 3'‐ C ‐hydroxymethyl‐3'‐ O ‐phosphonomethyl‐β‐ d ‐5'‐deoxyxylose nucleoside analogs in satisfying yield.