New synthetic pathways to C-glycosides

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 hav e shown the importance of the glycoside component of glycoproteins for cell recognition and differentiation processes. C-glycosidic analogues of that component would be meta-bolically stable, and thus offer enhanced therapeut ic value. Synthesis of a configurational variety of e.g. amino (glycopyrano syl) methanes is thus an important synthetic goal. The amino group would al low linking the C-glycoside to a variety of scaffolds. Our first approach h as been to C-link a C-N synthon (HCN or CH3NO2) 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, prepare d by a novel method. The catalytic hydrogenation of glycosyl cyanides prese nted challenges and new synthetic possibilities. With CH3NO2, and 4,6-O-alk ylidene 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-b eta-D-glycopyranosyl) methane with Fe-0/Ni-0 in THF/H2O/CO2 readily supplie d amino (4,6-O-benzylidene-beta-D-glucopyranosyl) methane, derivatives of w hich were diastereodiversified into D-allo, D-manno, and D-altro C-glycosid es. These approaches fail, however, if prerequisite natural carbohydrate pr ecursors are not available in a given case. Thus, a total synthesis scheme was also initiated. Phthalimido acetaldehyde diethylacetal and 4-penten-2-o l, with TiCl4, form 2-methyl-4-chloro-6-phthalimido-methyl tetrahydropyran, which was functionalized into phthalimido (6-deoxy-beta-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. (C) 1998 Elsevier Science Ltd. All righ ts reserved.