Synthesis of C-4′Truncated Phosphonated Carbocyclic 2′-Oxa-3′-azanucleosides as Antiviral Agents

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• 作者：Anna Piperno ; Salvatore V. Giofr ; Daniela Iannazzo ; Roberto Romeo ; Giovanni Romeo ; Ugo Chiacchio ; Antonio Rescifina ; Dorota G. Piotrowska
• 刊名：Journal of Organic Chemistry
• 出版年：2010
• 出版时间：May 7, 2010
• 年：2010
• 卷：75
• 期：9
• 页码：2798-2805
• 全文大小：861K
• 年卷期：v.75,no.9(May 7, 2010)
• ISSN：1520-6904

文摘

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 α-nucleosides as the main adducts. On the other hand, the target β-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 β-anomers of TPCOANs are able to inhibit the reverse trancriptase of different retroviruses at concentrations in the nanomolar range, with a potency comparable with that of tenofovir.