Synthesis of glycosyl(thio)ureido sugars via carbodiimides and their conformational behaviour in water.

The preparation of sugar ureas and thioureas by nucleophilic addition of water or hydrogen sulfide, respectively, to sugar-derived carbodiimides has been examined. Acetic acid efficiently catalysed the formation of ureas, whereas silica gel was found to be a more convenient catalyst in the case of the thioxo analogues. The procedures have been exploited in the development of an amine- and isocyanate-free synthesis of urea- and thiourea-tethered pseudooligosaccharides via the corresponding glycosylcarbodiimido sugars. The fully unprotected compounds adopted, preferentially, the (Z,Z) configuration at the pseudoamide bonds in water solution.

Generalized anomeric effect in action: synthesis and evaluation of stable reducing indolizidine glycomimetics as glycosidase inhibitors.

A series of aminoketalic castanospermine analogues incorporating a stereoelectronically anchored axial hydroxy group at the pseudoanomeric stereocenter (C-5) have been synthesized to satisfy the need for glucosidase inhibitors that are highly selective for alpha-glucosidases. The polyhydroxylated bicyclic system was built from readily available hexofuranose derivatives through a synthetic scheme that involved (i) the construction of a five-membered cyclic (thio)carbamate or (thio)urea moiety at the nonreducing end and (ii) the intramolecular nucleophilic addition of the heterocyclic thiocarbamic nitrogen atom to the masked aldehyde group of the monosaccharide. A biological screening of the resulting reducing 2-oxa- and 2-azaindolizidines against several glycosidase enzymes is reported.