4-C-Me-DAB and 4-C-Me-LAB-enantiomeric alkyl-branched pyrrolidine iminosugars-are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group

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.