Solid-Phase Synthesis of 5'-O-β,γ-Methylenetriphosphate Derivatives of Nucleosides and Evaluation of Their Inhibitory Activity Against HIV-1 Reverse Transcriptase.
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.
Ahmadibeni
Yousef
Y
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, Rhode Island 02881, USA.
Dash
Chandravanu
C
Le Grice
Stuart F J
SF
Parang
Keykavous
K
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