New Synthetic Pathways to C-Glycosides

TLDR: In this paper, the synthesis of C-glycopyranosyl compounds has been studied in the context of cell recognition and differentiation processes, and the first approach has been to link a C-N synthon (HCN or CH 3 NO 2 ) to the anomeric carbon of a natural carbohydrate.

Abstract: C-glycopyranosyl compounds exhibit antimicrobial, antifungal, and antitumor activities, most probably based on enzyme inhibition or interference with cell surface recognition phenomena. Recent developments in glycobiology have shown the importance of the glycoside component of glycoproteins for cell recognition and differentiation processes. C-glycosidic analogues of that component would be metabolically stable, and thus offer enhanced therapeutic value. Synthesis of a configurational variety of e.g. amino (glycopyranosyl) methanes is thus an important synthetic goal. The amino group would allow linking the C-glycoside to a variety of scaffolds. Our first approach has been to C-link a C-N synthon (HCN or CH 3 NO 2 ) to the anomeric carbon of a natural carbohydrate. We have realized this with cyanide on glycal, on per-O-acetyl sugars and on cyclic acetal protected glycosyl fluorides, prepared by a novel method. The catalytic hydrogenation of glycosyl cyanides presented challenges and new synthetic possibilities. With CH 3 NO 2 , and 4,6-O-alkylidene protected D-glucose or D-mannose derivatives, we obtained very good yields of cyclic Henry condensation products in THF with a novel catalytic procedure. The novel reduction of the resulting nitro (4,6-O-benzylidene-β-D-glycopyranosyl) methane with Fe 0 /Ni 0 in THF/H 2 O/CO 2 readily supplied amino (4,6-O-benzylidene-β-D--glucopyranosyl) methane, derivatives of which were diastereodiversified into D-allo, D-manno, and D-altro C-glycosides. These approaches fail, however, if prerequisite natural carbohydrate precursors are not available in a given case. Thus, a total synthesis scheme was also initiated. Phthalimido acetaldehyde diethylacetal and 4-penten-2-ol, with TiCl 4 , form 2-methyl-4-chloro-6-phthalimido-methyl tetrahydropyran, which was functionalized into phthalimido (6-deoxy-β-D,L-hexopyranosyl) methanes. Chiral extensions of this method are possible. C-'disaccharides' became available from the Ferrier 'dimerisation' of glycals, and from the hydrogenation of glycosyl cyanides.