¹H- and ¹³C-n.m.r. studies of N-methyl-1-deoxynojirimycin, an α-d-glucosidase inhibitor

The ¹³C-{¹H}-n.m.r. spectra (acidic D₂O, pD ∼1) of N-methyl-1-deoxynojirimycin (1,5-dideoxy-1,5-methyliminium-d-glucitol), an inhibitor of processing α-d-glucosidases involved in glycopeptide biosynthesis, showed two isomers (∼11:1 ratio) differing in the stereochemistry of the N⁺DCH₃ group. Assignments of carbon absorbances were made by ¹H-¹³C heterocorrelation 2D n.m.r. spectroscopy, and DEPT techniques. For the minor (axial N-methyl group) species, the chemical shifts of the ring carbons in 1,4 position to the methyl group (and of the methyl carbon atom itself) were shifted characteristically upfield relative to the absorbances for the corresponding carbon atoms in the major (equatorial N-methyl) species. Two N⁺DCH₃ singlets, in an ∼11:1 ratio, were also noted in the slow-exchange limit (SEL) ¹H-n.m.r. spectrum recorded for a solution in acidic aqueous medium (pD ∼1). Vicinal proton-proton coupling constants were consistent with a chair conformation for the SEL cationic major species, and for the free base at the fast exchange limit. The 5-hydroxymethyl gauche-gauche rotamer of the cationic equatorial N-methyl diastereomer (and of the free base) was found to be strongly preponderant [≥90%] in aqueous solution.