Synthesis of nucleoside 5′-O-α,β-methylene-β-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase

Authors

Yousef Ahmadibeni, University of Rhode Island
Chandravanu Dash
Michael J. Hanley, University of Rhode Island
Stuart F.J. Le Grice
Hitesh K. Agarwal, University of Rhode Island
Keykavous Parang, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

2010

Department

Biomedical and Pharmaceutical Sciences

Abstract

A polymer-bound α,β-methylene-β-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5′-O-α,β-methylene-β-triphosphates. Among all the compounds, cytidine 5′-O-α,β-methylene-β-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a K_i value of 225 μM.

Citation/Publisher Attribution

Ahmadibeni, Y., Dash, C., Hanley, M. J., Le Grice, S. F. J., Agarwal, H. K., & Parang, K. (2010). Synthesis of nucleoside 5′-O-α,β-methylene-β-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase. Organic & Biomolecular Chemistry, 8(6), 1271-1274. doi:

Available at: http://dx.doi.org/10.1039/B922846B