Mannosazide Methyl Uronate Donors. Glycosylating Properties and Use in the Construction of β-ManNAcA-Containing Oligosaccharides

Abstract

Mannosazide methyl uronate donors equipped with a variety of anomeric leaving groups (β- and α-S-phenyl, β- and α-N-phenyltrifluoroacetimidates, hydroxyl, β-sulfoxide, and (R(s))- and (S(s))-α-sulfoxides) were subjected to activating conditions, and the results were monitored by (1)H NMR. While the S-phenyl and imidate donors all gave a conformational mixture of anomeric α-triflates, the hemiacetal and β- and α-sulfoxides produced an oxosulfonium triflate and β- and α-sulfonium bistriflates, respectively. The β-S-phenyl mannosazide methyl uronate performed best in both activation experiments and glycosylation studies and provided the 1,2-cis mannosidic linkage with excellent selectivity. Consequently, an α-Glc-(1→4)-β-ManN(3)A-SPh disaccharide, constructed by the stereoselective glycosylation of a 6-O-Fmoc-protected glucoside and β-S-phenyl mannosazide methyl uronate, was used as the repetitive donor building block in the synthesis of tri-, penta-, and heptasaccharide fragments corresponding to the Micrococcus luteus teichuronic acid.

Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

“…α‐Thioglycosides and analogous α‐sulfoxides of S ‐phenyl mannoazide uronate donors were also shown to exist primarily in the 1 C 4 confirmation, as opposed to the corresponding β‐thioglycoside/sulfoxide anomers that adopt a 4 C 1 chair in line with the observations made for xylopyranosyl sulfoxides.…”

Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry

“…56 On gaining an insight into the reaction mechanism, it was concluded that when thiophenyl donor 37 is activated in the presence of diphenyl sulfoxide and triflic anhydride, anomeric triflate 38 is formed (Scheme 5). The latter exists as an interchangeable mixture of conformers with the 1 C 4 chair as the predominant species.…”

Pre‐Activation‐Based Stereoselective Glycosylations

“…It is challenging to form this linkage as it is thermodynamically less stable than the corresponding 1,2‐ trans linkage due to the anomeric effect and the steric hindrance posted by the C2 substituent in glycosylation. The van der Marel group developed a series of 2‐azido mannosyluronate donors bearing various anomeric leaving groups including thioether, sulfoxide and trifluoroacetimidate (donors 170 – 176 ) . Under the pre‐activation protocol, all these glycosyl donors gave good 1,2‐ cis selectivities.…”