226988-19-8Relevant articles and documents
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.
Alves, M. Jose,Costa, Flora T.,Duarte, Vera C. M.,Fortes, Antonio Gil,Martins, Jose A.,Micaelo, Nuno M.
scheme or table, p. 9584 - 9592 (2012/01/03)
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.
Improvements to the synthesis of isofagomine, noeuromycin, azafagomine, and isofagomine lactam, and a synthesis of azanoeuromycin and guanidine isofagomine
Meloncelli, Peter J.,Stick, Robert V.
, p. 827 - 833 (2007/10/03)
Improvements in the preparation of a key imidazylate and the reduction of the derived nitrile have led to more efficient syntheses of isofagomine, noeuromycin, azafagomine, and isofagomine lactam. As well, a precursor of azafagomine has been converted int
Enantiospecific synthesis of 1-azafagomine
Ernholt,Thomsen,Lohse,Plesner,Jensen,Hazell,Liang,Jakobsen,Bols
, p. 278 - 287 (2007/10/03)
For the first time the two enantiomeric forms of the glycosidase inhibitor 1-azafagomine have been synthesised starting from D- and L-xylose. D-Xylose was converted to the 2,3,5-tribenzylfuranose, which upon reductive amination with tert-butyl carbazate gave the protected 1-hydrazino-1- deoxypentitol in high yield. N-acetylation, mesylation of the 4-OH, removal of the Boc group, cyclisation and deprotection gave (+)-1-azafagomine ((+)- 1). By a similar sequence of reactions, L-xylose was converted to (-)-1- azafagomine ((-)1). Enzymatic and other routes to optically pure 1- azafagomine were also studied. Compound (-)-1 is a potent competitive glycosidase inhibitor, while (+)-1 has no biological activity. The inhibition of almond β-glucosidase by (-)-1 was found to be slow owing to a slow binding step of inhibitor to enzyme, with no subsequent conformational rearrangement. The rate constants for binding and release were found to be 3.3 x 104 M-1 s-1 and 0.011 s-1, respectively, yielding K(i) = 0.33 μM.
Chemoenzymatic synthesis of enantiopure 1-azafagomine
Liang, Xifu,Bols, Mikael
, p. 8485 - 8488 (2007/10/03)
A new chemoenzymatic synthesis of both enantiomeric forms of the glycosidase inhibitor 1-azafagomine (1) is reported. The synthesis starts from the achiral starting materials pentadienol and methylurazol with the key steps being a hetero-Diels-Alder reaction followed by a lipase R/Novozym 435- catalyzed enantioselective esterification of the Diels-Alder adduct.
