Development of voglibose (Basen(R)), an antidiabetic agent

Voglibose (1, N-[2-hydroxy-1-(hydroxymethyl)ethyl] valiolamine, basen®), having more potent disaccharidase inhibitory activity against maltase and sucrase than do naturally occurring pseudo-oligosaccharide α-glucosidase inhibitors, has been developed for the treatment of diabetes mellitus as the blood glucose ameliorating agent. Valiolamine (2), an important key compound for the preparation of N-substituted valiolamine derivatives such as 1, was synthesized by stereoselective hydration of the carbon-carbon double bond of valienamine (3) obtained by microbiological degradation of validamycins. Efficient and practical total synthesis of 2 starting from D-glucose has also been achieved. In animals and healthy volunteers, voglibose (1) significantly reduced postprandial blood glucose concentration. Clinical trials in patients with diabetes mellitus also demonstrated that 1 improves post-pratial glucose levels. In Japan, 1 was approved in July, 1994.