Synthesis and .alpha.-D-glucosidase inhibitory activity of N-substituted valiolamine derivatives as potential oral antidiabetic agents

Various kinds of N-substituted valiolamine derivatives, including compounds 23a, 24a, and 34a, which are structurally analogous to the key pseudodisaccharides (25a and 26a) of naturally occurring oligosaccharide alpha-D-glucosidase inhibitors, have been synthesized and estimated by the measure of inhibitory activity against porcine sucrase and maltase. The N-substituted valiolamine derivatives evaluated in this study have been found to be more potent than the corresponding N-substituted valienamine derivatives as well as the parent valiolamine. It is noteworthy that even simple N-substituted valiolamine derivatives such as N-[2-hydroxy-1-(hydroxymethyl)ethyl]-, N-[(1R,2R)-2-hydroxycyclohexyl]-, and N-[(R)-(-)-beta-hydroxyphenethyl]valiolamine (6, 8a, and 9a) have the stronger alpha-D-glucosidase inhibitory activity against porcine intestinal maltase and sucrase than naturally occurring oligosaccharide alpha-D-glucosidase inhibitors.