Journal of the American Chemical Society, Vol.133, No.48, 19524-19535, 2011
Synthetic Study and Structural Analysis of the Antifreeze Agent Xylomannan from Upis ceramboides
The novel antifreeze factor, xylomannan, first isolated from the freeze-tolerant Alaskan beetle Upis ceramboides, demonstrates a high degree of thermal hysteresis, comparable to that of the most active insect antifreeze proteins. Although the presence of a lipid component in this factor has not yet been verified, it has been proposed that the glycan backbone consists of a beta-D-mannopyranosyl-(1 -> 4)-beta-D-xylopyranose-disaccharide-repeating structure according to MS and NMR analyses. In this contribution, we report the stereoselective synthesis of the tetrasaccharide beta-D-mannopyranosyl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 4)-beta-D-mannopyranosyl-(1 -> 4)-D-xylopyranoside, a structural component of xylomannan. Our synthesis features the use of 2-naphthylmethyl (NAP)-ether-mediated intramolecular aglycon delivery (IAD) as the key reaction in obtaining beta-mannopyranoside stereoselectively. Various donors for NAP-IAD were tested to determine the most suitable for the purposes of this synthesis. Fragment coupling between a disaccharyl fluoride and a disaccharide acceptor obtained from a common beta-D-mannopyranosyl-(1 -> 4)-beta-D-xylopyranoside derivative was successfully carried out to afford the desired tetrasaccharide in the presence of Cp2HfCl2-AgClO4. Structural analysis of the resulting synthetic tetrasaccharide using NMR techniques and molecular modeling was performed in order to demonstrate the presence of the proposed xylomannan linkages in this molecule.