Advances in the Synthesis of Homochiral (-)-1-Azafagomine and (+)-5-epi-1-Azafagomine. 1-N-Phenyl Carboxamide Derivatives of both Enantiorners of 1-Azafagomine: Leads for the Synthesis of Active alpha-Glycosidase Inhibitors.

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Jose Alves, MJ (Author) Other; Costa, FT (Author) Other; Duarte, VCM (Author) Other; Fortes, AG (Author) Other; Martins, JA (Author) Other; Micaelo, NM (Author) Other

Journal

Title: Journal of Organic Chemistry

Vol. 76

Pages: 9584-9592

ISSN: 0022-3263

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-002-HSR

DOI: 10.1021/jo201486q

Abstract (EN): 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's 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 toward baker's yeast a-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by a-glucosidase from baker's yeast was studied by molecular modeling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic subsite (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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9