Premium
Synthesis and Antiviral Evaluation of 3'‐ C ‐Hydroxymethyl‐3'‐ O ‐Phosphonomethyl‐β‐D‐5'‐deoxyxylose Nucleosides
Author(s) -
Ji Shujie,
Wang Song,
Wang Haixia,
Gao Yingying,
Xu Wenke,
Huo Xiangyu,
Herdewijn Piet,
Liu FengWu
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000831
Subject(s) - chemistry , phosphonate , hydroxymethyl , dihydroxylation , nucleoside , stereochemistry , nucleoside analogue , yield (engineering) , stereoselectivity , aldose , enantioselective synthesis , organic chemistry , catalysis , glycoside , materials science , metallurgy
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.