Spirohydantoins from D-ribose as new potent enzymatic inhibitors

Abstract

Anomeric spirohydantoin derivatives from monosaccharides are known for various biological properties. We describe herein the synthesis of the 3-spirohydantoin derivatives of D-allose and D-ribose. The key step is the stereoselective glyco-alpha-aminonitrile formation from ulose derivatives of D-glucose and D-xylose using titanium tetra-isopropoxide as a mild and efficient catalyst. Target compounds were synthesized from these intermediates. The glucidic moiety was partially or totally deprotected under acidic conditions. These new heterocyclic monosaccharidic derivatives are potent glycogen phosphorylase inhibitors.

Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

“…C-2, 62, 63 C-3,[64][65][66][67][68][69][70][71][72] and C-473,74 hydantoin derivatives (highlighted in red in 20, Figure 5) have been synthesised and biologically evaluated in the past 10-15 years. Representative examples of this class of glycosidase inhibitor are highlighted in Figure 5.…”