Glycosidase inhibitors, glucose

Rare or unnatural monosaccharides have many useful applications as nonnutritive sweeteners, glycosidase inhibitors and so on. For example, L-glucose and L-fructose are known to be low-calorie sweeteners. In addition, rare or unnatural monosaccharides are potentially useful as chiral building blocks for the synthesis of biologically active compounds. Therefore, these compounds have been important targets for the development of enzymatic synthesis based in the use of DHAP-dependent aldolases alone or in combination with isomerases. Fessner et al. showed that rare ketose-1-phosphates could be reached not only by aldol addition catalyzed by DHAP-dependent aldolases, but by enzymatic isomerization/ phosphorylation of aldoses [35]. Thus, for example, L-fructose can be prepared... 

Glycosidase inhibitors (Table 1.9) delay the digestion of dietary carbohydrate in the form of starch and sucrose into monosaccharides, which can be absorbed from the small intestine. By delaying absorption, these agents lower postprandial blood glucose and insulin levels and are used for this purpose in the treatment of type 2 diabetes. 

Figure 7 Glycosidase inhibitors that are being tested against diabetes. Acarbose is an inhibitor of amylases and inhibits utilization of starch and glycogen thereby lowering blood glucose levels. Other inhibitors may also have potential use by inhibiting key glycosidases, or other enzymes, that are involved in raising blood glucose levels.

Wrodnigg et developed an original synthetic approach to the glycosidase inhibitors 93, which starts with 5-azido-5-deoxy-D-glucose (91) and proceeds through die intermediate 5-azido-5-deoxy-D-fiuctosamines (92) (Scheme 44). 

D-Glucose and L-arabinose have been converted into l,3-diamino-l,3-dideoi -D-direitol and D-erythritol respectively as potential glycosidase inhibitors. The same paper also describes the preparation of unusual urea and thiourea derivatives such as 21 and 22 also as potential glycosidase inhibitors. 

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