title: Synthesis of S-linked thiooligosaccharide analogues of Nod factors: synthesis of new protected thiodisaccharide and thiotrisaccharide intermediates.
abstract: We are investigating the synthesis of thioanalogues of nodulation factors that will be resistant to degradation by chitinases. To study the influence of our protecting group strategy, the glycosylation of 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside (7) with two trichloroacetimidate glycosyl donors carrying an azido group at C-2 and either benzyl or benzoyl protecting groups on O-3 and O-4 was first attempted under catalysis with BF(3).Et(2)O in toluene. While glycosylation with the benzoylated glycosyl donor gave only a poor yield (27%) of the disaccharide, a similar reaction with the benzylated donor gave the corresponding disaccharide in good yield (77%). Although both products were obtained as anomeric mixtures, the benzylated donor led to improved stereoselectivity in favor of the desired beta-anomer (alpha:beta 3:7). Based on these results, a novel thiotrisaccharide was synthesized via the coupling of 7 with 6-O-acetyl-4-S-(3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D-glucopyranosyl)-2-azido-3-O-benzyl-2-deoxy-4-thio-alpha-D-glucopyranosyl trichloroacetimidate (25) also newly synthesized. After optimization of the reaction conditions, the desired thiotrisaccharide 4-O-[6-O-acetyl-4-S-(3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D-glucopyranosyl)-2-azido-3-O-benzyl-2-deoxy-4-thio-beta-D-glucopyranosyl]-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside (26beta) was obtained in 57% yield. These conditions led to an anomeric mixture in favor of the desired beta-anomer (alpha:beta 1:4.7) that was separated from the alpha-anomer by normal-phase HPLC on a PrepNova Pack(R) silica gel cartridge. The work described here shows that thiodisaccharide glycosyl donors behave quite differently from the analogous O-disaccharide used previously to synthesize nodulation factors.
authors.affiliation: Laboratoire de Chimie des Hétérocycles et des Glucides, Ecole Nationale Supérieure de Chimie de Clermont-Ferrand, BP 187, F-63174, Aubière, France.
authors.forename: Latino Loureiro
authors.initials: LL
authors.lastname: Morais
authors.forename: Khalil
authors.initials: K
authors.lastname: Bennis
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ripoche
authors.forename: Liang
authors.initials: L
authors.lastname: Liao
authors.forename: France-Isabelle
authors.initials: FI
authors.lastname: Auzanneau
authors.forename: Jacques
authors.initials: J
authors.lastname: Gelas
mesh_terms: D002240:Carbohydrate Sequence; D002686:Chitin / Q000031:analogs & derivatives; D004187:Disaccharides / Q000138:chemical synthesis; D006031:Glycosylation; D008070:Lipopolysaccharides / Q000737:chemistry*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D014312:Trisaccharides / Q000138:chemical synthesis
chemical_list: D004187:Disaccharides; D008070:Lipopolysaccharides; C092736:Nod factor, Rhizobium leguminosarum; D009844:Oligosaccharides; D013865:Thioglycosides; D014312:Trisaccharides; D002686:Chitin