Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/15141
Título: | Advances in the synthesis of Homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: leads for the synthesis of active α-Glycosidase inhibitors |
Autor(es): | Alves, M. José Costa, Flora Teixeira e Duarte, Vera C. M. Fortes, A. Gil Martins, J. A. R. Micaelo, N. M. |
Palavras-chave: | Diels-Alder Iminosugars 1-azafagomine derivatives Glycosidase inhibitors Synthesis |
Data: | 2011 |
Editora: | American Chemical Society (ACS) |
Revista: | The Journal of Organic Chemistry |
Resumo(s): | - A new expeditious preparation of homochiral (-)-1-azafagomine, and (+)-5-epi-1-azafagomine has been devised. Stoodley´s diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione, was merged with Bols protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition towards baker´s yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker´s yeast was studied by molecular modelling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic sub-site (pocket) in the enzyme´s active site, seems to be responsible for the improved binding affinity in relation to underivatized (-)1-azafagomine and (+)1-azafagomine. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/15141 |
DOI: | 10.1021/jo201486q |
ISSN: | 0022-3263 1520-6904 |
Versão da editora: | http://pubs.acs.org/ |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CDQuim - Artigos (Papers) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Vera-JOC-2011.pdf | manuscript | 1,36 MB | Adobe PDF | Ver/Abrir |