The regioisomeric cycloadducts of the bromonitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene were easily prepared and elaborated into a novel class of uracil nor-nucleoside derivatives. In the key-synthetic step represented by the reductive N-O bond cleavage, an unusual double ring opening afforded the aminol intermediates containing a β-hydroxynitrile structure. By adapting known protocols, the aminols entered the linear construction of uracil rings. These novel nucleosides were found structurally similar to a potent antiviral compound, Brivudin, and molecular modeling and docking allowed to select one of the two regioisomeric structures as promising candidate for antiviral tests, due to the nice level of binding with the Thymidine Kinase, the enzyme involved in virus replication.

Savion, M., Memeo, M., Bovio, B., Grazioso, G., Legnani, L., Quadrelli, P. (2012). Synthesis and molecular modeling of novel dihydroxycyclopentane-carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition. TETRAHEDRON, 68(7), 1845-1852 [10.1016/j.tet.2011.12.086].

Synthesis and molecular modeling of novel dihydroxycyclopentane-carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition

LEGNANI, LAURA;
2012

Abstract

The regioisomeric cycloadducts of the bromonitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene were easily prepared and elaborated into a novel class of uracil nor-nucleoside derivatives. In the key-synthetic step represented by the reductive N-O bond cleavage, an unusual double ring opening afforded the aminol intermediates containing a β-hydroxynitrile structure. By adapting known protocols, the aminols entered the linear construction of uracil rings. These novel nucleosides were found structurally similar to a potent antiviral compound, Brivudin, and molecular modeling and docking allowed to select one of the two regioisomeric structures as promising candidate for antiviral tests, due to the nice level of binding with the Thymidine Kinase, the enzyme involved in virus replication.
Articolo in rivista - Articolo scientifico
1,3-Dipolar cycloaddition; Bromonitrile oxide; Molecular docking; Nor-nucleosides; Thymidine kinase;
English
1845
1852
8
Savion, M., Memeo, M., Bovio, B., Grazioso, G., Legnani, L., Quadrelli, P. (2012). Synthesis and molecular modeling of novel dihydroxycyclopentane-carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition. TETRAHEDRON, 68(7), 1845-1852 [10.1016/j.tet.2011.12.086].
Savion, M; Memeo, M; Bovio, B; Grazioso, G; Legnani, L; Quadrelli, P
File in questo prodotto:
File Dimensione Formato  
TET_12_Br.pdf

Solo gestori archivio

Dimensione 1.03 MB
Formato Adobe PDF
1.03 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/351932
Citazioni
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 16
Social impact