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

Abstract

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.

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water extractable phytochemicals from some tropical spices

“…This action may pose an advantage over synthetic drugs presently in use for the management of postprandial blood glucose, such as acarbose, which strongly inhibit α-amylase. There are indications that excessive pancreatic amylase inhibition could result into abnormal bacterial fermentation of undigested saccharides in the colon (Horii et al, 1986;Bischoff, 1994). Hence, stronger inhibition of α-glucosidase activity and mild inhibition of α-amylase activity of the spice extracts could minimize the major setback of currently used α-glucosidase and α-amylase inhibitory drugs with side effects such as abdominal distention, flatulence, meteorism and possibly diarrhea (Bischoff, 1994).…”

α-Glucosidase Inhibitory Activity of a 70% Methanol Extract from Ezoishige (Pelvetia babingtoniide Toni) and Its Effect on the Elevation of Blood Glucose Level in Rats

“…Therefore, an inhibitor of intestinal a-glucosidase could be expected to retard carbohydrate digestion and absorption. Potent a-glucosidase inhibitors such as acarbose 1) and voglibose 2) have already been clinically used as medicines for diabetic and obese patients.…”

Biosynthesis and Biological Activity of Carbasugars

“…Conversely, valiolamine (34) has more potent -glucosidase inhibitory activity against porcine intestinal sucrase, maltase, and isomaltase than the rest of the aminocarbasugars [311]. This is why series of N-substituted valiolamines were synthesized, resulting in the preparation of the glycohydrolase inhibitor voglibose (48) [312][313][314]. Voglibose was launched as an antidiabetic agent in 1994 to improve postprandial hyperglycemia in diabetes mellitus [315][316][317][318].…”