Synthesis of Neoglycoconjugates Containing 4‐Amino‐4‐deoxy‐L‐arabinose Epitopes Corresponding to the Inner Core of Burkholderia and Proteus Lipopolysaccharides

Abstract

Disaccharides that contain 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and d-glycero-d-talo-oct-2-ulosonic acid (Ko) substituted at the 8-position by 4-amino-4-deoxy-β-l-arabinopyranosyl (Ara4N) residues have been prepared. Coupling an N-phenyltrifluoroacetimidate-4-azido-4-deoxy-l-arabinosylglycosyl donor to acetyl-protected allyl glycosides of Kdo and Ko afforded anomeric mixtures of disaccharide products in 74 and 90 % yield, respectively, which were separated by chromatography. Further extension of an intermediate Ara4N-(1→8)-Kdo disaccharide acceptor, which capitalized on a regioselective glycosylation with a Kdo bromide donor under Helferich conditions, afforded the branched trisaccharide α-Kdo-(2→4)[β-l-Ara4N-(1→8)]-α-Kdo derivative. Deprotection of the protected di- and trisaccharide allyl glycosides was accomplished by TiCl4-promoted benzyl ether cleavage followed by the removal of ester groups and reduction of the azido group with thiol or Staudinger reagents, respectively. The reaction of the anomeric allyl group with 1,3-propanedithiol under radical conditions afforded the thioether-bridged spacer glycosides, which were efficiently coupled to maleimide-activated bovine serum albumin. The neoglycoconjugates serve as immunoreagents with specificity for inner core epitopes of Burkholderia and Proteus lipopolysaccharides.

Efficient Perovskite Solar Cells with 13.63 % Efficiency Based on Planar Triphenylamine Hole Conductors

“…In this molecule, the core Kdo moiety is substituted, respectively, at C4 and C8 by an α‐Kdo residue and a 4‐amino‐4‐deoxy‐β‐ L ‐arabinose (Ara4N) subunit. Although the preparation of the trisaccharide sequence was previously fulfilled by Kosma et al., the total synthetic efficiency was very low owing to the poor regioselectivity observed in the coupling reaction of the peracetylated Kdo bromide donor with the Ara4N‐Kdo disaccharide 4,5,7‐triol acceptor 4g. Here, we envisioned that the use of the 4,8‐orthogonally protected Kdo donor 1 c would facilitate the construction of such 4,8‐branched skeleton.…”

“…Thus, upon activation with TBPA, 1 c was condensed with allyl alcohol to exclusively yield the α‐monosaccharide glycoside 8 in 87 % yield. After removal of the C8 Nap group of 8 with 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) in a mixture of CH 2 Cl 2 and CH 3 OH, the obtained Kdo alcohol 9 was reacted with the Ara4N N ‐phenyltrifluoroacetimidate donor 10 4g in a CH 2 Cl 2 /Et 2 O (1:1) co‐solvent in the presence of TMSOTf (0.03 equiv) to give the disaccharide 11 in 90 % yield as a separable 1:1.5 α/β mixture. Then, subjecting pure β‐ 11 to Zemplén transesterification (NaOMe, MeOH) gave 12 , which contains a free 4‐OH group (92 % yield).…”

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

“…For the future synthesis of deprotected glycal ester derivatives containing prenyl units, benzyl groups will have to be exchanged for protecting groups that can be removed under nonhydrogenolytic conditions, e.g., silyl ether protecting groups. In preliminary experiments, Lewis acid cleavage using BBr 3 , BCl 3 , and TiCl 4 , respectively, was not successful, although the latter reagent had previously been used to deprotect two benzyl groups from an allyl glycoside containing a 4-amino-4-deoxy-ʟ-arabinose residue [36]. Cleavage of the benzyl protecting groups with concomitant reduction of the azido group afforded the α-anomeric octyl ((4-amino-4-deoxyʟ-arabinopyranosyl)methyl)phosphonate 16 in 38% yield.…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…Analysis of commercial sample for measurement of hydrodynamic volume (Plesner et al, 2011) GM3 (Neu5Ac-2 3-Gal-1 4-Glc) As possible oligosaccharideconjugate vaccine (Oberli et al, 2011) Inner core of Burkholderia and Proteus LPS BSA TOF (sinapinic) Containing 4-amino-4-deoxy-Larabinose epitopes as immunoreagents (Blaukopf et al, 2012) Inner core oligosaccharide of Moraxella catarrhalis Diphtheria toxin, CRM 197 TOF (sinapinic) Use of three conjugation methods.…”