The synthesis of a differentially protected oxygenated pyrroline nitrone and its application in routes to hyacinthacine family alkaloids

Abstract

Glycosidases are involved in a range of important biological processes. The possibility of blocking or modifying these processes using glycosidase-inhibiting sugar mimics for therapeutic or biotechnological applications has attracted much interest. This may have significance in the treatment of cancer, viral infections, diabetes and obesity. Iminosugars are analogues of mono- or disaccharides where the ring oxygen is replaced by a nitrogen atom. These compounds include polyhydroxylated derivatives of monocyclic structures such as piperidines and pyrrolizidines, and also of bicyclic structures such as indolizidines and pyrrolizidines. Routes to nitrone 190 from L-xylose and D-arabinose were explored and the application of nitrone 190 towards the synthesis to hyacinthacine A1 and hyacinthacine B2 were investigated. The differential protection of the C-3 position of nitrone 190 meant that this position would be selectively deprotected after cycloaddition, liberating the C-1 hydroxyl group (hyacinthacine numbering) as a site for inversion. Inversion of the hydroxyl group would then provide the required stereochemical outcome for hyacinthacines A1 and B2, where the stereochemistry at C-1 and C-2 is cis