Synthesis and antiviral activity of fluoro-substituted apio dideoxynucleosides.
Novel fluoro-substituted apio dideoxynucleosides ((+/-)-3a and (+/-)-3b) were efficiently synthesized starting from 1,3-dihydroxyacetone via Horner-Emmons olefination as a key step. Cyclization of fluoro ester (+/-)-6 under acidic conditions to the fluorolactone was smoothly proceeded in favor of trans-fluorolactone due to the favorable transition state with equatorial hydroxymethyl substituent. Unfortunately, the final nucleosides (+/-)-3a and (+/-)-3b were found to be inactive against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV.
Hong
J H
JH
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul, Korea.
Kim
H O
HO
Moon
H R
HR
Jeong
L S
LS
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013056:Spectrophotometry, Ultraviolet; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides