Regiospecific anomerisation of acylated glycosyl azides and benzoylated disaccharides by using TiCl4

Abstract

Chelation induced anomerisation is promoted when Lewis acids, such as TiCl4 or SnCl4, coordinate to the pyranose ring oxygen atom and another site, giving rise to endocyclic cleavage and isomerisation to the more stable anomer. In this research regiospecific site-directed anomerisation is demonstrated. TiCl4 (2.5 equiv) was employed to induce anomerisation of 15 glycosyl azide and disaccharide substrates of low reactivity, and high yields (>75%) and stereoselectivies (α/β>9:1) were achieved. The examples included glucopyranuronate, galactopyranuronate and mannopyranuronate as well as N-acetylated glucopyranuronate and galactopyranuronate derivatives. A disaccharide with the α1→4 linkage found in polygalacturonan was included. The use of benzoylated saccharides was found to be important in disaccharide anomerisation as attempts to isomerise related acetyl protected and 2,3-carbonate protected derivatives were not successful.

Keywords: Lewis acids; anomerisation; glycuronic acid; protecting groups; regioselectivity.