226988-06-3Relevant academic research and scientific papers
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.
Synthesis of (+)-azafagomine from D-xylose
Ernholt, Bettina V.,Thomsen, Ib B.,Jensen, Kenneth B.,Bols, Mikael
, p. 701 - 704 (2007/10/03)
L-glucose resembling enantiomer of the racemic glycosidase inhibitor azafagomine was synthesised from D-xylose and found to be inactive.
