title: Synthesis and antiretroviral activity of novel 4'-fluoro-5'-deoxyphosphonic acid carbocyclic nucleoside analogs.
abstract: Novel 5'-deoxycarbocyclic purine phosphonic acid analogs with the 4'-electropositive moiety, fluorine were designed, and synthesized from glyceraldehyde. The cyclopentenol intermediate, 9, was successfully synthesized by the ring-closing metathesis of divinyl 8. The condensation reaction of cyclopentanol 15 with purine bases under Mitsunobu conditions successfully afforded the desired phosphonate analogs. The synthesized nucleoside phosphonic acid analogs, 19, 22, 26, and 29, were subjected to antiviral screening against human immunodeficiency virus (HIV)-1. Guanine phosphonic acid analog 29 showed significant anti-HIV activity (EC50 = 10.3 μM).
authors.affiliation: a BK-21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Seyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000146:Acids, Carbocyclic; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005461:Fluorine / Q000737:chemistry; D005985:Glyceraldehyde / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011685:Purine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000598519:9-((4'-fluoro-4'-ethylcyclopentan-1'-yl)guanine)phosphonic acid; D000146:Acids, Carbocyclic; D019380:Anti-HIV Agents; D063065:Organophosphonates; D011685:Purine Nucleotides; D005461:Fluorine; D005985:Glyceraldehyde; D006147:Guanine
keywords: 4′-fluoro-5′-deoxyphosphonic acid analog; Anti-HIV agent; Mitsunobu reaction; carbocyclic nucleoside