Solid-phase synthesis of 5′-O-β,γ-methylenetriphosphate derivatives of nucleosides and evaluation of their inhibitory activity against HIV-1 reverse transcriptase

Authors

Yousef Ahmadibeni, University of Rhode Island
Chandravanu Dash
Stuart F.J. Le Grice
Keykavous Parang, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

2010

Department

Biomedical and Pharmaceutical Sciences

Abstract

Bis(dichlorophosphino)methane was converted to a β,γ-methylenetriphosphitylating reagent. The reagent was immobilized on aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford a polymer-bound β,γ-methylenetriphosphitylating reagent, which was reacted with unprotected nucleosides followed by oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and acidic cleavage to produce 5′-O-β,γ-methylene triphosphate nucleosides in 53–82% overall yields. Among all the compounds, cytidine 5′-O-β,γ-methylenetriphosphate inhibited completely RNase H activity of HIV-1 reverse transcriptase at 700 μM.

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Citation/Publisher Attribution

Ahmadibeni, Y., Dash, C., Le Grice, S. F.J., & Parang, K. (2010). Solid-phase synthesis of 5′-O-β,γ-methylenetriphosphate derivatives of nucleosides and evaluation of their inhibitory activity against HIV-1 reverse transcriptase. Tetrahedron Letters, 51(22), 3010-3013. doi: 10.1016/j.tetlet.2010.04.005

Available at: https://doi.org/10.1016/j.tetlet.2010.04.005

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.