Advances in the Synthesis of Homochiral (鈭?-1-Azafagomine and (+)-5-epi-1-Azafagomine. 1-N-Phenyl Carboxamide Derivatives of both Enantiomers of 1-Azafagomine: Leads for the Synthesis of

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• 作者：M. Jos茅 Alves ; Flora T. Costa ; Vera C. M. Duarte ; Antonio Gil Fortes ; Jos茅 A. Martins ; Nuno M. Micaelo
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：December 2, 2011
• 年：2011
• 卷：76
• 期：23
• 页码：9584-9592
• 全文大小：458K
• 年卷期：v.76,no.23(December 2, 2011)
• ISSN：1520-6904

文摘

A new expeditious preparation of homochiral (鈭?-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 伪-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by 伪-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 (鈭?-1-azafagomine and (+)-1-azafagomine.