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

Yousef Ahmadibeni, Chandravanu Dash, Stuart F J Le Grice, Keykavous Parang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3010-3013
Number of pages4
JournalTetrahedron Letters
Volume51
Issue number22
DOIs
StatePublished - Jun 2 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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