Synthesis of novel 4'-cyclopropyl-5'-norcarbocyclic adenosine phosphonic acid analogues.
Novel 4'-cyclopropyl-5'-norcarbocyclic adenosine phosphonic acid analogues were designed and racemically synthesized from propionaldehyde 5 through a de novo acyclic stereoselective route using triple Grignard addition and ring-closing metathesis (RCM) as key reactions. To improve cellular permeability and enhance the anti-HIV activity of this phosphonic acid, SATE phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine phosphonic acids analogues 17, 18, 19, 21, and 23 were subjected to antiviral screening against HIV-1. Compound 23 exhibits enhanced anti-HIV activity than its parent nucleoside phosphonic acid 18.
BK-21 Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Guang Huan
GH
Shen
Joon Hee
JH
Hong
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry
D000447:Aldehydes; D019380:Anti-HIV Agents; D003517:Cyclopentanes; D009705:Nucleosides; D063065:Organophosphonates; D000255:Adenosine Triphosphate; C005556:propionaldehyde