Synthesis of alpha- and beta-D-(1-->6)-C-Disaccharides by Wittig Olefination of Formyl C-Glycosides with Glycopyranose 6-Phosphoranes.

Abstract

The synthesis of (1-->6)-C-disaccharides by Wittig condensation of formyl C-glycofuranosides and pyranosides with galacto- and glucopyranose 6-phosphoranes is described herein. The method involves the coupling of the sugar aldehydes with the ylides and the reduction of the double bond of the resulting sugar alkenes, in most of the cases by catalytic hydrogenation. The reduction with nickel boride or diimide is employed in some special cases. O-Benzyl protective groups are removed by catalytic hydrogenation either in the course of the reduction of the double bond or in a subsequent step, while O-isopropylidene groups are cleaved by treatment with Amberlite IR-120. In this way, eight free beta-D-(1-->6)-C-disaccharides have been prepared in 26-61% overall yield starting from beta-linked formyl C-glycosides. These include C-linked analogues of the biologically active disaccharides allolactose (Galbeta1,6Glc), gentiobiose (Glcbeta1,6Glc), and N-acetylamino disaccharides (GalNHAcbeta1,6Gal and GalNHAcbeta1,6Glc). Moreover, the synthesis of two alpha-D-(1-->6)-C-disaccharides is described from formyl C-furanosides. The limiting condition of the synthesis of these stereoisomers is the configurational instability of the alpha-linked formyl C-glycosides under the basic conditions of the Wittig olefination.