Stereoselective synthesis of nonsymmetrical difructose dianhydrides from xylylene-tethered d-fructose precursors

Abstract

Nonsymmetrical furanose–pyranose difructose dianhydrides (DFAs), a class of cyclic disaccharides present in foodstuffs, have been prepared in high yield by connecting the reacting monosaccharide moieties through a xylylene bridge prior to triflic acid-promoted bis-spiroketalization. The reaction can then proceed either intra- or intermolecularly, both the regio- and the stereoselectivity being strongly dependent on the spacer length. Noteworthy, the longer m- and p-xylylene positional isomers led to the thermodynamic α-d-fructofuranose β-d-fructopyranose 1,2′:2,1′-dyanhydride 1, the major DFA in commercial caramel, in a stereoselective manner. The shorter o-xylylene tether afforded preferentially the elusive contra-thermodynamic β-d-fructofuranose α-d-fructopyranose diastereomer 2, a trace constituent of caramel. The results have been rationalized in terms of stereoelectronic and conformational properties and offer new perspectives for the preparation of pure DFA standards for analytical and nutritional studies.