Synthesis of [4,5-Bis(hydroxymethyl)-1,3-dioxolan-2-yl]nucleosides as Potential Inhibitors of HIV
- 1 January 1996
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (11) , 3599-3603
- https://doi.org/10.1021/jo960008k
Abstract
The synthesis of 1,3-dioxolan-2-ylnucleosides and related chemistry is described. We have shown that 2-methoxy-1,3-dioxolane (6) reacts with silylated thymine and trimethylsilyl triflate to give the acyclic formate ester 1-[2-(formyloxy)ethyl]thymine (8) rather than 1-(1,3-dioxolan-2-yl)thymine (7). A tentative mechanism which could explain this result is discussed. On the other hand, 2-methoxy-1,3-dioxolane 13c reacts with silylated bases to give [4,5-bis(hydroxymethyl)-1,3-dioxolan-2-yl]nucleosides, thus representing the first examples of this novel class of compounds. The nature of the nucleobase and the hydroxyl protecting groups was found to have great influence on the reaction and on the stability of the nucleosides. Compounds 16 and 18 were found to be inactive when tested for anti HIV-1 activity in vitro.Keywords
This publication has 32 references indexed in Scilit:
- Synthesis of L-Dioxolane Nucleosides and Related ChemistryThe Journal of Organic Chemistry, 1995
- A New Synthesis of 4-Thiofuranosides via Regioselective Opening of an Episulfide with Allylmagnesium BromideThe Journal of Organic Chemistry, 1994
- Photocatalysed addition of alcohols to 5-substituted 2,5-dihydrofuran-2-ones: novel synthesis of (3′R)-2′,3′-dideoxy-3′-hydroxymethyl nucleosidesJournal of the Chemical Society, Perkin Transactions 1, 1994
- Antiviral optically pure dioxolane purine nucleosides analoguesBioorganic & Medicinal Chemistry Letters, 1993
- Synthesis and Antiviral Evaluation of 3′-Branched Nucixoside AnaloguesNucleosides and Nucleotides, 1991
- Heats of formation of 1,3-dioxolenium ions from ortho ester precursors in sulfuric acid solution: methyl vs. phenyl substitution at the pro-acyl carbon atomThe Journal of Organic Chemistry, 1984
- Chemical conversion of thymidine into 5-methyl-2′-deoxycytidineJournal of the Chemical Society, Chemical Communications, 1981
- 1,3-Dioxolan-2-ylium and related heterocyclic cationsChemical Reviews, 1972
- Über 1.3‐Dioxolane, I. Darstellung von 2‐Alkoxy‐1.3‐dioxolanenEuropean Journal of Inorganic Chemistry, 1958
- Steroids. LXXIII.1a The Direct Oppenauer Oxidation of Steroidal Formate Esters. A New Synthesis of 17α-Hydroxyprogesterone1bJournal of the American Chemical Society, 1956