Concise Synthesis of the Hexasaccharide Repeating Unit of the Capsular Polysaccharide of Klebsiella K19 Strain

Abstract

A convergent [4+2] stereoselective block glycosylation strategy has been developed for the synthesis of the hexasaccharide repeating unit of the capsular polysaccharide of Klebsiella K19 strain in very good yield. The p-methoxybenzyl (PMB) group was used as a temporary alkyl protecting group, which was removed by tuning the glycosylation conditions. A thioglycoside was used as a glycosyl acceptor in an orthogonal glycosylation reaction. A late-stage TEMPO-mediated selective oxidation of a primary hydroxyl group into carboxylic acid allowed incorporation of the d-glucuronic acid moiety in the hexasaccharide. A combination of N-iodosuccinimide (NIS) and perchloric acid supported over silica (HClO4–SiO2) was used as a thiophilic promoter for the activation of thioglycosides. HClO4–SiO2 was also used as a solid acid activator for a glycosyl trichloroacetimidate derivative.

Convenient Synthesis of the Branched Hexasaccharide Repeating Unit of the Cell Wall O-Antigen of Escherichia coli O80 Strain

“…The disaccharide thioglycoside also can be synthesized by applying stereoand regioselective 'armed-disarmed' glycosylation 17 of L-fucose-derived thioglycoside donor 5 with D-glucosamine-derived thioglycoside acceptor diol 6. The key features of the synthetic strategy are: (a) stereo-and regioselective sequential and block glycosylations to achieve the branched hexasaccharide; (b) application of 'armed-disarmed' glycosylation using thioglycosides; 17 (c) preparation of a D-galactosamine derivative from a suitably protected D-glucosamine intermediate; 18 (d) conversion of an amino group into the azido functionality by azido transfer; 19 (e) late stage TEMPO-mediated oxidation of a primary hydroxyl group into the carboxylic acid keeping a secondary hydroxyl group unaffected; 20 (f) a reasonably good yield of glyco-sylation with satisfactory stereochemical outcome; and (g) the use of the p-methoxyphenyl (PMP) group as anomeric protecting group at the reducing end, which could be removed by treatment with ammonium cerium nitrate (CAN) 21 to provide a hemiacetal derivative for the functionalization of the glycan into a possible glycoconjugate derivative.…”