Total Synthesis of theEscherichia coliO111O‐Specific Polysaccharide Repeating Unit

Abstract

The first total synthesis of the O-antigen pentasaccharide repeating unit from Gram-negative bacteria Escherichia coli O111 was achieved starting from four monosaccharide building blocks. Key to the synthetic approach was a bis-glycosylation reaction to combine trisaccharide 10 and colitose 5. The colitose building block (5) was obtained de novo from non-carbohydrate precursors. The pentasaccharide was equipped at the reducing end with an amino spacer to provide a handle for subsequent conjugation to a carrier protein in anticipation of immunological studies.

Detailed Investigation of the Immunodominant Role of O‐Antigen Stoichiometric O‐Acetylation as Revealed by Chemical Synthesis, Immunochemistry, Solution Conformation and STD‐NMR Spectroscopy for Shigella flexneri 3a

“…The transformation of a trichloroacetamide to its parent acetamide has been accomplished with a variety of methods . In particular, late‐stage Pd/C‐mediated conversion concomitant to final benzyl ether hydrogenolysis is an attractive option, which, however, has some limitations, as demonstrated in this work. Indeed, the present results— 11 → 12 (75 %), 16 →[ 3 , 17 (49 and 4 %, respectively)], 24 →[ 4 , 26 (52 and 10 %, respectively)], 28 →[ 1 , 30 , 31 , 32 (28, 6, 18, and 7 %, respectively)]—point to the chloroacetamide‐to‐acetamide conversion as being the rate‐limiting step in the formation by this method of SF3a saccharides larger than one repeating unit.…”

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

“…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 . Owing to the 2 C ‐O‐acetylation of the target compounds, we were limited to reductive conditions for the NHCOCCl 3 →NHAc conversion.…”

Regioselective Benzylation of 2‐Deoxy‐2‐aminosugars using Crown Ethers: Application to a Shortened Synthesis of Hyaluronic Acid Oligomers

“…Sometimes, due to incompatibilities amongst certain protecting groups, the 3‐ O ‐protecting group needs to be swapped, thereby leading to an even longer route. For example, in the recently reported synthesis of an E. coli O111 O ‐specific polysaccharide repeating unit, a 4,6‐di‐ O ‐benzyl NHTCA substrate with SEt as the anomeric protecting group and Fmoc (fluorenylmethyloxycarbonyl) as the 3‐ O protecting group was synthesized in 7 steps from per‐acetylated NHTCA substrate 23. The steps for the currently employed methods are long, and in our hands, we obtained highly variable results using the reported non‐basic benzylation methods on carbohydrate substrates.…”