Allyl Glycosides Research Articles

Synthesis of neoglycoproteins containing L-glycero-α-D- manno-heptopyranosyl-(1→4)- and -(1→5)-linked 3-deoxy-α-D-manno-oct-2- ulopyranosylonic acid (Kdo) phosphate determinants

The disaccharide allyl glycosides 4, 8, 13 and the trisaccharide 33 have been prepared using heptopyranosyl trichloroacetimidate 1 or the disaccharide bromide 27 as glycosyl donors followed by efficient O-phosphorylation via the amidite procedure. The allyl glycosides 4, 8 and 33 are converted into 3-(2-aminoethylthio)propyl glycosides and are coupled to bovine serum albumin. The resulting neoglycoconjugates 6 and 35 containing spacer-linked Hep-(1→4)-Kdo and Hep-(1→5)-Kdo 4-phosphate-(2→6)-β-GlcNAc residues correspond to part structures of the inner core region in bacterial lipopolysaccharide, whereas compound 10 contains the artificial analogue Hep-(1→4)-Kdo 5-phosphate. The compounds may be used in immunochemical characterisation of monoclonal antibodies.

Vinyl glycosides in oligosaccharide synthesis (part 4): glycosidase-catalysed preparation of substituted allyl glycosides

But-3-en-2-yl glycosides have been obtained by glycosidase-catalysed transformations under thermodynamic conditions, and reaction parameters have been optimised. It has been shown that the enzymes can be immobilised on non-ionic Amberlite resin (XAD-4) and can conveniently be retrieved and re-used in a subsequent glycosylation. The enzyme-catalysed reactions display some diastereodifferentiation with a preference for the (R)- over the (S)-alcohol. An increase in size of the aliphatic substituent on the allyl alcohol gives a significant improvement of diastereoselection.

Structural requirements of synthetic oligosaccharides to bind monoclonal antibodies against Chlamydia lipopolysaccharide.

Monoclonal antibodies were generated against a synthetic glycoconjugate containing the trisaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo (Kdo, 3-deoxy-D-manno-2-octulopyranosonic acid) which represents the genus-specific epitope of the lipopolysaccharide from the obligatory intracellular human pathogen Chlamydia. Antibodies of all immunoglobulin G isotypes were obtained and characterized by enzyme immunobinding and inhibition assays using the immunizing antigen as well as chemically synthesized derivatives of the Kdo trisaccharide. The latter contained (1) one of the three residues in beta- instead of alpha-linkage, (2) a Kdo residue the carboxyl group of which had been reduced to a CH2OH group (Kdo(C1-red)), or (3) changing the linkage of the terminal Kdo from 2-->8 to 2-->4. Only one compound, namely, alpha-Kdo-(2-->8)-alpha-Kdo(C1-red)-(2-->4)-alpha-Kdo exhibited binding to and inhibition of Kdo trisaccharide-specific antibodies, whereas all other compounds were not active. Structural and conformational investigations using NMR spectroscopy at high field on the allyl glycosides of the oligosaccharides 6-12 confirmed the conformational similarities between those structures 4, 5, and 10 which were able to bind to the antibodies investigated.

Preparation of antigens and immunoadsorbents corresponding to the Streptococcus group a cell-wall polysaccharide

The allyl glycosides of a tri-, penta- and hexasaccharide corresponding to the Streptococcus Group A cell-wall polysaccharide were coupled to solid or soluble supports to give immunoaffinity columns and neoglycoproteins, respectively. Cysteamine hydrochloride was added to the allyl glycosides and the resulting cysteamine adducts were used for subsequent coupling to linkers via the amine functionality. The tri- and penta- saccharide cysteamine adducts were coupled directly to the azalactone-derivatized 3M Emphase TM Biosupport Medium AB 1 to yield two affinity columns. The penta- and hexa- saccharides were coupled to bovine serum albumin or ovalbumin via the conjugate addition of the ϵ-amino groups of lysines on the proteins with the N-acryloylated sugars or the oligosaccharide-squarate adducts, derived in turn from the cysteamine adducts. The efficiency of the above methods is compared.

Efficient, convergent syntheses of oligosaccharide allyl glycosides corresponding to the Streptococcus group A cell-wall polysaccharide

Convergent syntheses of di-, tri, tetra-, penta-, and hexa-saccharide allyl glycosides corresponding to the β-hemolytic Streptococcus Group A cell-wall polysaccharide are described. The strategy relies on the preparation of related di- and tri-saccharide building blocks: β- d -Glc p NAc-(1–3)-α- l -Rha p and α- l -Rha p -(1–2)-[(β- d -Glc p NAc-(1–3)]-α- l -Rha p , which could be used either as glycosyl donors or acceptors in subsequent glycosylation reactions. The protecting groups were chosen to allow the selective removal of the allyl aglycon to access the intermediate glycosyl donors but also to allow their own removal without affecting the allyl group. The allyl group was intended for use in conjugation of the oligosaccharides to soluble protein carriers or solid supports for the preparation of antigens and immunoadsorbents, respectively.

Efficient, convergent syntheses of oligosaccharide allyl glycosides corresponding to the Streptococcus Group A cell-wall polysaccharide

Convergent syntheses of di-, tri, tetra-, penta-, and hexa-saccharide allyl glycosides corresponding to the β-hemolytic Streptococcus Group A cell-wall polysaccharide are described. The strategy relies on the preparation of related di- and tri-saccharide building blocks: β- d-Glc pNAc-(1–3)-α- l-Rha p and α- l-Rha p-(1–2)-[(β- d-Glc pNAc-(1–3)]-α- l-Rha p, which could be used either as glycosyl donors or acceptors in subsequent glycosylation reactions. The protecting groups were chosen to allow the selective removal of the allyl aglycon to access the intermediate glycosyl donors but also to allow their own removal without affecting the allyl group. The allyl group was intended for use in conjugation of the oligosaccharides to soluble protein carriers or solid supports for the preparation of antigens and immunoadsorbents, respectively.

One-step glycosylation and selective deprotection of peracetylated monosaccharides for facile syntheses of allyl glycosides with a free C-2 hydroxyl group

One-step glycosylation and selective deprotection of peracetylated monosaccharides for facile syntheses of allyl glycosides with a free C-2 hydroxyl group

Synthesis of neoglycoproteins containing 5-O-phosphorylated Kdomonosaccharide, 4-O- and 5-O-phosphorylated α-Kd↬(2 6)-2-acetamido-2-deoxy- -D-glucopyranosyl disaccharide residues

Radical addition of cysteamine to anomeric allyl glycosides of Kdo 5-phosphates 1 and 4 afforded good yields of the corresponding 3-(2-aminoethylthio)propyl glycosides. Similar reactions with the α-allyl glycoside of Kdo 4-phosphate 7 led to substantial formation of the dephosphorylated product 10 through intramolecular hydrolysis of the 4-O-phosphomonoester by the terminal amino function of the spacer group. Similar side reactions occurred upon deblocking of the 4- O-phosphorylated 6-aminohexyl-α-glycoside lactone derivative 18. Allyl glycosides of 4'- O- and 5'- O-phosphorylated Kd↬ (2 6)-glucosamine derivatives were prepared in good yields via phosphorylation using the amidite procedure. The 4'-phosphate moiety was introduced following intramolecular protection of the 5'-OH group as a lactone. Subsequent deprotection gave the allyl glycosides 25 and 33 which were transformed into the corresponding stable spacer derivatives 26 and 34 by coupling with cysteamine. The ligands were activated with thiophosgene and reacted with bovine serum albumin to give the neoglycoconjugates 3, 6, 27 and 35 to be used in immunochemical studies of monoclonal antibodies directed against Haemophilus influenzae Re-mutant and related lipopolysaccharides.

Vinyl Glycosides in Oligosaccharide Synthesis. 2. The Use of Allyl and Vinyl Glycosides in Oligosaccharide Synthesis

A novel latent-active glycosylation strategy has been described that relies on the isomerization of substituted allyl glycosides to give the corresponding vinyl glycosides, which can subsequently be used in Lewis acid-mediated glycosylations. The isomerization reaction was performed by a rhodium catalyst obtained by treating tris(triphenylphosphine)rhodium(I) chloride with n-butyllithium. This catalyst has many advantageous properties over the use of conventional Wilkinson's catalyst. The glycosylation reactions gave high yields for both primary and secondary sugar alcohols, and the anomeric selectivity could be controlled by the constitution of the glycosyl donor and reaction conditions. The new isomerization and glycosylation approach enables complex oligosaccharides of biological importance to be prepared in a highly convergent manner.

Synthesis of a tetrasaccharide fragment of the circulating anodic antigen of Schistosoma mansoni

A stereocontrolled synthesis of the allyl glycoside of a tetrasaccharide fragment of the O-linked polysaccharide chain of the circulating anodic antigen of Schistosoma mansoni, β- d-Gl cp A-(1→3)-β- d-Gal p NAc-(1→6)-[β- d-Gl cp A- (1→3)-β- d-Gal p NAc , is presented.

Synthesis of Kdo-trisaccharide derivatives of chlamydial and enterobacterial LPS containing carboxyl-reduced or β-configurated Kdo-residues

Five allyl glycosides corresponding to the 3-deoxy-D- manno-2-octulosonic acid (Kdo) containing genus-specific LPS epitope of Chlamydia were synthesized. Compounds 5 and 22 contain one carboxyl-reduced Kdo moiety linked to O-4 of the proximal Kdo unit, whereas the analogues 28, 34 and 36 each contain one β-linked Kdo-residue within the trisaccharide sequence Kdo p-(2→8)-Kdo p-(2→4)-Kdo p. Elaboration of the carboxyl-reduced derivatives was achieved by BF3•Et2O-catalyzed coupling of Kdo-fluoride derivatives 1 or 14 with the 7,8- O-carbonyl-derivative 2. The β-linked oligosaccharides were obtained by Helferich-glycosidation of the respective Kdo-disaccharide bromide derivatives 26 and 31. The deprotected compounds - characterized by H and13C NMR spectroscopy - are suitable haptens for the immunochemical study of monoclonal antibodies directed against the Kdo-region of chlamydial and enterobacterial LPS.

Synthetic Glycoconjugates. 4. Use of .omega.-(Acrylamido)alkyl Glycosides for the Preparation of Cluster Glycopolymers

A simple and efficient method for the syntheses of clustering-sugar homopolymers from ω-(acrylamido)allyl glycosides of N-acetyl-β-D-glucosamine (GlcpNAc) is described. Radical polymerization of the new glycosides proceeded smoothly in an aqueous solution in the presence of ammonium persulfate and TMEDA and gave water-soluble homopolymers having high-density sugar branches as a novel class of cluster glycosides. The apparent association constant of wheat germ agglutinin (WGA) with poly[3-(N-acryloylamino)propyl 2-acetamido-2-deoxy-β-D-glucopyranoside] was determined by measuring the change in fluorescence intensity produced by various concentrations of polymeric ligand and found to be approximately 10 8 M -1

Vinyl glycosides in oligosaccharide synthesis (part 1): A new latent-active glycosylation strategy

We have developed a novel latent-active glycosylation strategy. This glycosylation strategy is based on isomerisation of substituted allyl glycosides to give vinyl glycosides which can subsequently be used in a Lewis acid mediated glycosylation reaction. This approach will enable complex oligosaccharides of biological importance to be prepared in a highly convergent manner.

Synthesis of Neoglycoproteins as Artificial Antigens

Abstract The synthesis of various allyl glycosides of L-rhamnose containing ether and/or ester substituents are reported. Ozonolysis of allyl glycosides followed by reductive amination with ∊-amino groups of lysine residues in bovine serum albumin using sodium cyanoborohydride at pH 7.8 provided different structural neoglycoproteins as artificial antigens.

ChemInform Abstract: Anomeric O‐Alkylation. Part 11. Anomeric O‐Alkylation of O‐Unprotected Hexoses and Pentoses ‐ Convenient Synthesis of Decyl, Benzyl, and Allyl Glycosides.

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A new method for the cleavage of allyl glycosides

Allyl glycosides can be cleaved by Wacker oxidation followed by photolysis in the presence of triethylamine.

Anomeric O‐alkylation, 11. Anomeric O‐Alkylation of O‐Unprotected Hexoses and Pentoses – Convenient Synthesis of Decyl, Benzyl, and Allyl Glycosides

AbstractThe base‐promoted reaction of O‐unprotected aldoses 1–6 with didecyl sulfate in DMPU affords decyl glycosides 1aα–6aα and 1aβ, 3aβ–6aβ in good overall yields. Similarly, the treatment of O‐unprotected hexoses 1–4 and pentoses 5 and 6 with benzyl bromide and allyl bromide yields after subsequent O‐acetylation monosaccharides 1cα–6cα, 1cβ, 3cβ–6cβ and 1dα–6dα, 1dβ, 3dβ–6dβ, respectively. The regio‐ and stereoselectivity in these reactions was determined by 1H‐NMR spectroscopic data of the O‐acetylated derivatives.

Bausteine von Oligosacchariden, CVI. Darstellung synthetischer Antigene von LD‐Heptose‐haltigen Trisacchariden der Core‐Region von Lipopolysacchariden durch Copolymerisation mit Acrylamid

Building Units of Oligosaccharides, CVI. – Preparation of Synthetic Antigens Composed of LD‐Heptose‐Containing Trisaccharides of the Core Region of Lipopolysaccharides by Copolymerization with AcrylamideThe allyl glycosides of the trisaccharide L‐α‐D‐Hep‐(1→3)‐α‐D‐Hep‐(1→5)‐Kdo in the α form 3 and β form 6 and furthermore of L‐α‐D‐Hep‐(1→7)‐L‐α‐D‐Hep‐(1→3)‐L‐α‐D‐Hep in the α form 20 were synthesized. The allyl glycosides were coupled with a cysteamin spacer in a radical‐addition reaction followed by an acylation with acryloyl chloride. The products could be copolymerized with acrylamide to afford the polymers 21, 22 and 23 with the trisaccharide structure as an immunological determinant.

Structures of the glycopeptidolipid antigens of serovars 25and 26 of the Mycobacterium aviumserocomplex, synthesis of allyl glycosides of the outer disaccharide units and serology of the derived neoglycoproteins

The pentasaccharide hapten released from the glycopeptidolipid (GPL) antigen of M. auium serovar26 has been characterized as O-(2,4-di- O-methyl- α- l-fucopyranosyl)-(1 → 4)- O- β- d-gluco-pyranosyluronic acid-(1 → 4)- O-(2- O-methyl- α- l-fucopyranosyl)-(1 → 3)- α- l-rhamnopyranosyl-(1 #x02192; 2)-6-deoxy- l-talose. The allyl glycosides of the outer glycosyl and glycobiosyl units of this hapten have been synthesized, the latter by a route involving oxidation of the corresponding d-glucopyranose derivative. Conjugation of allyl glycosides to protein by ozonolysis and reductive coupling afforded neoantigens (neo 26−1 and 26−2), both of which interacted with antibodies to M. avium serovar 26. The terminal sugar residue of the pentasaccharide hapten of the serovar 25 GPL had been shown to have the galacto configuration on the basis of 1H- 13C NMR correlation spectroscopy, but absolute configurational assignment for the sugar awaited the synthesis, as for neo 26, of two glycobiosyl NGPs bearing the terminal sugar in the d and l enantiomeric forms, respectively. Only the glycobiosyl NGP bearing the terminal sugar as the d-enantiomer interacted with antibodies to M. avium serovar 25, thus providing evidence for the absolute configuration of the sugar, and showing that the complete oligosaccharide hapten has the structure, O-(4-acetamido-4,6-dideoxy-2- O-methyl- α- d-galactopyranosyl)-(1 → 4)- O-β- d-glucopyranosyluronic acid-(1 → 4)- O-(2- O-methyl- α- l-fucopyranosyl)-(1 → 3)- O-α- l-rhamnopyranosyl-(1 → 2)-6-deoxy- l-talose.

Synthesis of allyl glycosides for conversion into neoglycoproteins bearing epitopes of mycobacterial glycolipid antigens

Neoglycoproteins bearing key glycosyl substituents of several glycopeptidolipid antigens of pathogenic Mycobacterium species have been synthesized. Allyl glycosides of the terminal 6-deoxyhexose-containing units of the antigens were prepared, with appropriate ether and ester substituents in place. Ozonolysis of the allyl glycosides was then followed by reductive coupling with ε-amino groups of lysine residues in bovine serum albumin, using sodium cyanoborohydride at pH 7.8. The resulting neoglycoproteins emulated the antigenicity of the native molecule in several serological tests.