Synthesis of the Zwitterionic Repeating Unit of the O-Antigen from Shigella sonnei and Chain Elongation at Both Ends

Abstract

Shigella sonnei O-antigen features a zwitterionic disaccharide repeat encompassing two rare monosaccharides. The synthesis of the AB repeat and of trisaccharides ABA' and B'AB, which validates chain elongation at either end, is reported. All targets were synthesized using a postglycosylation oxidation strategy in combination with imidate chemistry. Precursors to residue A were obtained from L-glucose. The AAT (B) donor and acceptor were obtained from D-glucosamine. A one-step Pd(OH)2/C-mediated deprotection provided the propyl glycoside targets.

Efficient Iterative Synthesis of O‐Acetylated Tri‐ to Pentadecasaccharides Related to the Lipopolysaccharide of Shigella flexneri Type 3 a through Di‐ and Trisaccharide Glycosyl Donors

“…Accordingly, decasaccharide 37 and pentadecasaccharides 38 , 39 , and 40 , bearing a chloroacetamide moiety at all the inner glucosamine residues, appear to be the most probable intermediates in the final deprotection process leading to propyl glycosides 2 and 3 , respectively. We found, fortunately, that conditions suitable for the conversion of precursors containing three trichloroacetamide moieties into S. sonnei zwitterionic trisaccharides also worked very well for the aforementioned precursors. Indeed, subjecting monochlorinated 37 to H 2 in the presence of a large excess amount of Pd(OH) 2 /C with t BuOH/H 2 O as the solvent resulted in the total consumption of the former and in the isolation of desired decasaccharide 2 in a satisfactory 63 % yield following reverse‐phase HPLC (RP‐HPLC) purification.…”

“…The mixture of chlorinated pentadecasaccharides containing intermediates 38 , 39 , and 40 was also subjected to the same conditions albeit for a longer time to give desired propyl glycoside 3 in 36 % yield. On the basis of these encouraging results and achievements in the S. sonnei series, decasaccharides 28 / 29 were subjected to H 2 in the presence of Pd(OH) 2 /C and a combination of t BuOH/CH 2 Cl 2 /H 2 O. Monitoring the reaction by RP‐HPLC indicated no further progression after 1.5 days, whereas HRMS analysis revealed conversion of the starting alcohols into monochlorinated 37 as the sole product.…”

“…Over the past decades, the trichloroacetyl group has become an increasingly popular protecting group for amino sugars. The plethora of conditions available for the NHCOCCl 3 →NHAc conversion and their diversity has enabled either base‐catalyzed removal of the trichloroacetyl moiety and/or its direct reduction into NHAc in oligosaccharides containing multiple N ‐trichloroacetyl groups. Nevertheless, incomplete dehydrochlorination of the N ‐trichloroacetyl group is not without precedent, including in our hands .…”

O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry

“…With the purpose to obtain fragments of 7 for binding studies, intermediate 17 was subjected to hydrogenolysis. The reaction was completed after 2 days at 750 psi using t BuOH/DCM/H 2 O as solvent . Subsequent saponification, without isolation and purification of the intermediate methyl ester 22 , gave uronic acid 23 in an unimpressive yield (35–50 % over two steps, Scheme ).…”

Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial Glycoconjugates as Potential Vaccine Candidates

“…The ZPS of S. sonnei has a disaccharide repeating unit made up of two uncommon aminosugars, a 2-acetamido-2-deoxy- l -altruronic acid (residue A) and a 2-acetamido-4-amino-2,4,6-trideoxy- d -galactopyranose (AAT, residue B) which are 1,2-trans linked to one another [ 76 ]. Mulard and co-workers accomplished chemical synthesis of all the ZPS oligosaccharides of Shigella sonnei [ 76 ].…”