Synthesis of S-linked thiooligosaccharide analogues of Nod factors: synthesis of new protected thiodisaccharide and thiotrisaccharide intermediates

• Published in: Carbohydrate research Vol. 338; no. 13; pp. 1369 - 1379
• Main Authors: Morais, Latino Loureiro, Bennis, Khalil, Ripoche, Isabelle, Liao, Liang, Auzanneau, France-Isabelle, Gelas, Jacques
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.06.2003; Elsevier
• Subjects: Analogues; Biochemistry & Molecular Biology; Carbohydrate Sequence; Chemistry; Chemistry, Applied; Chemistry, Organic; Chitin - analogs & derivatives; Disaccharides - chemical synthesis; Glycosylation; Life Sciences & Biomedicine; Lipopolysaccharides - chemistry; Molecular Sequence Data; Nodulation factors; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Physical Sciences; Science & Technology; Thioglycosides - chemical synthesis; Thioglycosides - chemistry; Thiooligosaccharides; Trisaccharides - chemical synthesis; Nodulation factors; Glycosylation; Thiooligosaccharides; Analogues; analogues; NODULATION; glycosylation; thiooligosaccharides; nodulation factors; DERIVATIVES
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(03)00149-6

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-β- 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 2O 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 β-anomer (α:β 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-β- d-glucopyranosyl)-2-azido-3- O-benzyl-2-deoxy-4-thio-α- 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-β- d-glucopyranosyl)-2-azido-3- O-benzyl-2-deoxy-4-thio-β- d-glucopyranosyl]-1,6-anhydro-2-azido-3- O-benzyl-2-deoxy-β- d-glucopyranoside ( 26β) was obtained in 57% yield. These conditions led to an anomeric mixture in favor of the desired β-anomer (α:β 1:4.7) that was separated from the α-anomer by normal-phase HPLC on a PrepNova Pack® 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. Graphic