Synthesis of C-4'truncated phosphonated carbocyclic 2'-oxa-3'-azanucleosides as antiviral agents.
J Org Chem
; 75(9): 2798-805, 2010 May 07.
Article
en En
| MEDLINE
| ID: mdl-20394405
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Aza
/
Ácidos Carbocíclicos
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Inhibidores de la Transcriptasa Inversa
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Organofosfonatos
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Nucleósidos
Límite:
Humans
Idioma:
En
Revista:
J Org Chem
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA