Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/15141

TitleAdvances 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
Author(s)Alves, M. José
Costa, Flora Teixeira e
Duarte, Vera C. M.
Fortes, A. Gil
Martins, J. A. R.
Micaelo, N. M.
KeywordsDiels-Alder
Iminosugars
1-azafagomine derivatives
Glycosidase inhibitors
Synthesis
Issue date2011
PublisherAmerican Chemical Society (ACS)
JournalThe Journal of Organic Chemistry
Abstract(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.
TypeArticle
URIhttp://hdl.handle.net/1822/15141
DOI10.1021/jo201486q
ISSN0022-3263
1520-6904
Publisher versionhttp://pubs.acs.org/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:CDQuim - Artigos (Papers)

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