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Solid-Phase Synthesis of 5'-O-?,?-Methylenetriphosphate Derivatives of Nucleosides and Evaluation of Their Inhibitory Activity Against HIV-1 Reverse Transcriptase.

ABSTRACT: Bis(dichlorophosphino)methane was converted to a ?,?-methylenetriphosphitylating reagent. The reagent was immobilized on aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford a polymer-bound ?,?-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-?,?-methylene triphosphate nucleosides in 53-82% overall yields. Among all the compounds, cytidine 5'-O-?,?-methylenetriphosphate inhibited completely RNase H activity of HIV-1 reverse transcriptase at 700 ?M.

SUBMITTER: Ahmadibeni Y

PROVIDER: S-EPMC2864936 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Solid-Phase Synthesis of 5'-O-β,γ-Methylenetriphosphate Derivatives of Nucleosides and Evaluation of Their Inhibitory Activity Against HIV-1 Reverse Transcriptase.

Ahmadibeni Yousef Y Dash Chandravanu C Le Grice Stuart F J SF Parang Keykavous K

Tetrahedron letters 20100601 22

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% ov ...[more]

PMID: 20454539

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