Synthesis of novel 6'-spirocyclopropyl-5'-norcarbocyclic adenosine phosphonic Acid analogues as potent anti-hiv agents.

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.

Citation

Lian Jin Liu, Eunae Kim, Joon Hee Hong. Synthesis of novel 6'-spirocyclopropyl-5'-norcarbocyclic adenosine phosphonic Acid analogues as potent anti-hiv agents. Nucleosides, nucleotides & nucleic acids. 2011 Oct;30(10):784-97

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PMID: 21967289

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