Abstract
A new template of C-4'-truncated phosphonated nucleosides (TPCOANs) has been obtained in good yields according to two different routes which exploit the reactivity of a phosphonated nitrone. The one-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl nucleobases leads to the unnatural alpha-nucleosides as the main adducts. On the other hand, the target beta-anomers have been obtained in high yield by a two-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl acetate followed by nucleosidation reaction. The reactivity of the phosphonated nitrone has been investigated trough quantum mechanical DFT calculations at the B3LYP/D95+(d,p) theory level. Preliminary biological assays show that beta-anomers of TPCOANs are able to inhibit the reverse transcriptase of different retroviruses at concentrations in the nanomolar range, with a potency comparable with that of tenofovir.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acids, Carbocyclic / chemical synthesis*
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Acids, Carbocyclic / chemistry
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Acids, Carbocyclic / pharmacology
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Cell Line
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Cyclization
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Humans
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Molecular Structure
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Nitrogen Oxides / chemical synthesis
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Nucleosides / chemical synthesis*
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Nucleosides / chemistry
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Nucleosides / pharmacology
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology
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Quantum Theory
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Retroviridae / drug effects
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Retroviridae / enzymology
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Vinyl Compounds / chemical synthesis
Substances
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Acids, Carbocyclic
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Aza Compounds
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Nitrogen Oxides
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Nucleosides
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Organophosphonates
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Reverse Transcriptase Inhibitors
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Vinyl Compounds
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nitrones
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vinyl acetate