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
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...
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Published in | Journal of organic chemistry Vol. 76; no. 23; pp. 9584 - 9592 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
American Chemical Society
02.12.2011
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Subjects | |
Online Access | Get full text |
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Summary: | 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 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 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/jo201486q |