title: Synthesis of novel 6'-spirocyclopropyl-5'-norcarbocyclic adenosine phosphonic Acid analogues as potent anti-hiv agents.
abstract: Novel 5'-norcarbocyclic adenosine phosphonic acid analogues with 6'-electropositive moiety such as spirocyclopropane were designed and synthesized from the commercially available diethylmalonate 5. Regioselective Mitsunobu reaction proceeded in the presence of an allylic functional group at a low reaction temperature in polar cosolvent [dimethylformamide (DMF)/1,4-dioxane] to give purine analogue 15. To improve cellular permeability and enhance the anti-human immunodeficiency virus (HIV) activity of this phosphonic acid, a SATE phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine phosphonic acids analogues 18-21 and 23 were subjected to antiviral screening against HIV-1.
authors.affiliation: BK-21 Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
authors.forename: Lian Jin
authors.initials: LJ
authors.lastname: Liu
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008314:Malonates / Q000737:chemistry; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004146:Dioxanes; D008314:Malonates; D063065:Organophosphonates; D013141:Spiro Compounds; C498810:diethyl malonate; C025223:1,4-dioxane; D000241:Adenosine