Progress in Kdo-glycoside chemistry

Abstract

Glycosylation chemistry of 3-deoxy-D--oct-2-ulosonic acid units has been considerably developed within the last decade. This review covers major achievements with respect to improved yields and anomeric selectivity as well as suppression of the elimination side reaction via selection of dedicated protecting groups and appropriate activation of the anomeric center.

Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

“…Glycosylation reactions with glycosyl donors of Kdo suffer from lack of anomeric selectivity, low reactivity due the electron-withdrawing ester group and facile formation of elimination products such as glycal ester 16 . 24 A limited number of groups have successfully accomplished the challenging glycosylation of the unreactive axial 5-OH group at the proximal unit of the central bacterial Kdo disaccharide α- d -Kdo-(2 → 4)-α- d -Kdo. 25 The synthesis of the resulting 4,5-disubstituted oligosaccharides is further complicated by the facile formation of 1′ → 5 interlinked Kdo lactone derivatives under acidic conditions, which would then block glycoside formation.…”

Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike

“…Although the well-established per- O -acetylated Kdo bromide methyl ester 11 exerts low α-selectivity and is prone to facile elimination, leading to the corresponding 2,3-dehydro derivative, the glycosylation under Helferich conditions is nevertheless a robust approach. 24 Reaction of 6 equiv of donor 11 with the previously synthesized trisaccharide acceptor derivative 12 (16) in dry acetonitrile in the presence of a 4.5:1 mixture of Hg(CN) 2 /HgBr 2 in dichloromethane at room temperature gave regioselectively 68% of the α-linked tetrasaccharide 13 together with 11% of the corresponding β-anomer (Scheme 3). The anomeric mixture was resolved by column chromatography, and the anomeric configuration was assigned on the basis of the downfield shifted 1 H NMR signal of H-4 (5.25 ppm for 13 and 4.85 ppm for the β-anomer) as well as the 1 H NMR chemical shifts of the equatorial 3-deoxy protons (2.25 ppm for 13 and 2.41 ppm for the β-isomer).…”

Synthesis of the Core Oligosaccharides of Lipooligosaccharides from Campylobacter jejuni: A Putative Cause of Guillain–Barré Syndrome

“…To assemble target LOS mimics 1 and 2 , we chose a convergent approach, rather than a linear synthesis, as the target oligosaccharides contain sialoside and KDO glycosides in both α configurations, and they are known to be difficult to synthesize by stereocontrolled construction . Although many target molecule disconnection patterns were considered on the basis of retrosynthetic analysis, key disconnection points were determined with respect to the early construction of both α‐sialoside and α‐KDO glycoside (Figure ).…”

“…To assemble target LOS mimics 1 and 2,w ec hose ac onvergent approach, rather than al inear synthesis, as the target oligosaccharides contain sialoside and KDO glycosides in both a configurations, and they are known to be difficult to synthesize by stereocontrolled construction. [12,13] Although many target molecule disconnectionp atterns were considered on the basis of retrosynthetic analysis, key disconnectionp oints were determined with respectt ot he early constructiono fb oth a-sialoside and a-KDO glycoside ( Figure 2). The following building blocks were designed:1 )a ganglioside-core oligosaccharide containing a-sialoside, 2) ab ranched l-glycero-d-manno-heptose-containingi nner-core trisaccharide, and 3) ar educinge nd a-KDO residue with ac onjugation-ready amino linker,i ncorporating an artificial lipid moiety rather than natural lipid Aa tt he last stage.…”

“…The α‐KDO glycoside was formed by a successive two‐step reaction comprising α‐selective glycosidation with N ‐Cbz‐protected 6‐amino‐1‐hexanol followed by removal of the phenylselenyl group at the C3 position. For α‐selective glycosidation of 2,3‐ene derivative 6 (to afford 7 ), phenylselenyl trifluoromethanesulfonate (PhSeOTf) was chosen as a promoter, as Achiwa et al.…”