Author/Authors :
Cruz، نويسنده , , Filipa P. da and Newberry، نويسنده , , Scott and Jenkinson، نويسنده , , Sarah F. and Wormald، نويسنده , , Mark R. and Butters، نويسنده , , Terry D. and Alonzi، نويسنده , , Dominic S. and Nakagawa، نويسنده , , Shinpei and Becq، نويسنده , , Frederic and Norez، نويسنده , , Caroline and Nash، نويسنده , , Robert J. and Kato، نويسنده , , Atsushi and Fleet، نويسنده , , George W.J.، نويسنده ,
Abstract :
The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pKa of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase Ki 0.89 μM, IC50 0.41 μM) is a competitive—whereas 4-C-Me-LAB (for rat intestinal sucrase Ki 0.95 μM, IC50 0.66 μM) is a non-competitive—specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB—but not isoLAB—is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.
