Stereoselective synthesis of N-acetyl thiochitooligosaccharides. Different behaviours of methyl N-acetyl-α- and -β-thiochitobiosides during acetolysis

Abstract

A stereoselective synthesis of N-acetyl-thiochito-di-, -tri- and -tetra-saccharides is described. Coupling of methyl 2-acetamido-3,6-di-O-benzoyl-2-deoxy-4-O-triflyl-β-4 or -α-D-galactopyranoside 19 with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-β-D-glucopyranose 5 in the presence of cysteamine in DMF gave, after de-O-acylation, methyl N,N′-diacetyl-β-9 and -α-thiochitobioside 21, respectively. Different behaviours of peracetylated methyl β-10 and α-thiochitobioside 22 towards acetolysis with Ac₂O–AcOH–H₂SO₄ solution were observed, with the α-isomer giving acyclic sugar species together with the desired thiochitobiose peracetate 11, while the α-isomer gave exclusively the thiochitobiose peracetate 11. This remarkable difference between α- and β-glycosides was further demonstrated by comparative acetolysis of methyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-23 and -β-D-glucopyranoside 24. Methyl N,N′,N″-triacetylthiochitotriosides 29 and 30 were synthesized through conversion of N,N′-diacetylthiochitobiose peracetate 11 into N,N′-diacetyl-1,4-dithiochitobiose derivative 28, followed by its coupling with triflates 4 and 19 in the presence of cysteamine. Similarly, extension of the sugar chain to a higher homologue was achieved by converting methyl N,N′,N″-triacetylthiochitotrioside 30 into the N,N′,N″-triacetyl-1,4,4′-trithiochitotriose derivative 33, the coupling of which with triflate 19 in the presence of cysteamine provided the methyl N,N′,N″,N‴-tetraacetylthiochitotetraoside 34 after de-O-acylation.