Trisaccharide Donor Research Articles

A General Strategy for the Synthesis of 3,6‐Branched Gluco‐Oligosaccharides: Facile Synthesis of the Phytoalexin Elicitor Oligosaccharides.

Abstract A general method for the synthesis of 3,6-branched gluco-oligosaccharides has been developed. As a typical example of the method, the synthesis of the glucohexatose phytoalexin elicitor on a large scale was achieved via coupling of a trisaccharide donor with a trisaccharide acceptor. The donor and acceptor were prepared easily from 1,2:5,6-di- O -isopropylidene-α- d -glucofuranose, 2,3,4,6-tetra- O -benzoyl-α- d -glucopyranosyl trichloroacetimidate, and 6- O -acetyl-2,3,4-tri- O -benzoyl-α- d -glucopyranosyl trichloroacetimidate in a regio- and stereoselective manner. Higher oligosaccharides of the elicitor including the hepta-, nona-, dodeca- and tetradecasaccharides have also been readily synthesized by this strategy.

Synthesis of the methyl glycoside of a branched octasaccharide fragment specific for the Shigella flexneri serotype 2a O-antigen

An efficient synthesis of the methyl glycoside of a branched octasaccharide representative of Shigella flexneri serotype 2a O-specific polysaccharide is described. The synthesis is based on the use of the trichloroacetimidate methodology, and involves the condensation of a pentasaccharide acceptor and a trisaccharide donor as the key step.

Synthesis of Le x-neoglycoconjugate to study carbohydrate–carbohydrate associations and its intramolecular interaction

A straightforward synthetic strategy for the preparation of the Le x neoglycoconjugate (11,11′-dithio bis[undecanyl-β- d-galactopyranosyl-(1→4)-α- l-fucopyranosyl-(1→3)-2-acetamido-2-deoxy-β- d-glucopyranoside]) and methyl Le x glycoside starting from the same trisaccharide donor is reported. This donor represents a very useful precursor for the construction of Le x derivatives. The Le x neoglycoconjugate has allowed the preparation of polyvalent gold glyconanoparticles and self-assembled monolayers on gold. 1H NMR of the Le x neoglycoconjugates suggests an intramolecular Le x–Le x cis-interaction in water, which is destroyed by addition of methanol.

A general strategy for the synthesis of 3,6-branched gluco-oligosaccharides: facile synthesis of the phytoalexin elicitor oligosaccharides

A general method for the synthesis of 3,6-branched gluco-oligosaccharides has been developed. As a typical example of the method, the synthesis of the glucohexatose phytoalexin elicitor on a large scale was achieved via coupling of a trisaccharide donor with a trisaccharide acceptor. The donor and acceptor were prepared easily from 1,2:5,6-di- O-isopropylidene-α- d-glucofuranose, 2,3,4,6-tetra- O-benzoyl-α- d-glucopyranosyl trichloroacetimidate, and 6- O-acetyl-2,3,4-tri- O-benzoyl-α- d-glucopyranosyl trichloroacetimidate in a regio- and stereoselective manner. Higher oligosaccharides of the elicitor including the hepta-, nona-, dodeca- and tetradecasaccharides have also been readily synthesized by this strategy.

Synthesis of α-Man p-(1→2)-α-Man p-(1→3)-α-Man p-(1→3)-Man p, the tetrasaccharide repeating unit of Escherichia coli O9a, and α-Man p-(1→2)-α-Man p-(1→2)-α-Man p-(1→3)-α-Man p-(1→3)-Man p, the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3

The tetrasaccharide repeating unit of Escherichia coli O9a, α- d-Man p-(1→2)-α- d-Man p-(1→3)-α- d-Man p-(1→3)- d-Man p, and the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3, α- d-Man p-(1→2)-α- d-Man p-(1→2)-α- d-Man p-(1→3)-α- d-Man p-(1→3)- d-Man p, were synthesized as their methyl glycosides. Thus, selective 3-O-allylation of p-methoxyphenyl α- d-mannopyranoside via a dibutyltin intermediate gave p-methoxyphenyl 3- O-allyl-α- d-mannopyranoside ( 2) in good yield. Benzoylation (→ 3), then removal of 1- O-methoxyphenyl (→ 4), and subsequent trichloroacetimidation afforded the 3- O-allyl-2,4,6-tri- O-benzoyl-α- d-mannopyranosyl trichloroacetimidate ( 5). Condensation of 5 with methyl 4,6- O-benzylidene-α- d-mannopyranoside ( 6) selectively afforded the (1→3)-linked disaccharide 7. Benzoylation of 7, debenzylidenation, benzoylation, and deallylation gave methyl 2,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→3)-2,4,6-tri- O-benzoyl-α- d-mannopyranoside ( 11) as the disaccharide acceptor. Coupling of 11 with (1→2)-linked mannose disaccharide donor 17 or trisaccharide donor 21, followed by deacylation, furnished the target tetrasaccharide and pentasaccharide, respectively.

A facile regio- and stereoselective synthesis of mannose octasaccharide of the N-glycan in human CD2 and mannose hexasaccharide antigenic factor 13b

A highly concise and effective synthesis of the mannose octasaccharide of the N-linked glycan in the adhesion domain of human CD2 was achieved via TMSOTf-promoted selective 6-glycosylation of a trisaccharide 4,6-diol acceptor with a pentasaccharide donor, followed by deprotection. The pentasaccharide was constructed by selective 3,6-diglycosylation of 1,2- O-ethylidene-β- d-mannopyranose with 2- O-acetyl-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→2)-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl trichloroacetimidate, while the trisaccharide was obtained by selective 3-O -glycosylation of allyl 4,6- O-benzylidene-α- d-mannopyranoside with the same disaccharide trichloroacetimidate, followed by debenzylidenation. The mannose hexasaccharide antigenic factor 13b was synthesized by condensation of a trisaccharide donor, 2- O-acetyl-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→2)-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→3)-4,6-di- O-acetyl-2- O-benzoyl-α- d-mannopyranosyl trichloroacetimidate, with a trisaccharide acceptor, methyl 3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→2)-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→2)-3,4,6-tri- O-benzoyl-α- d-mannopyranoside, followed by deprotection.

Synthesis of a hexasaccharide that relates to the arabinogalactan epitope

A hexasaccharide derivative of the arabinogalactan epitope, methyl β- d-galactopyranosyl-(1→6)-[α- l-arabinofuranosyl-(1→3)]-β- d-galactopyranosyl-(1→6)-β- d-galactopyranosyl-(1→6)-[α- l-arabinofuranosyl-(1→3)]-α- d-galactopyranoside, was synthesized efficiently using a 3+3 strategy. The key step is the preparation of the trisaccharide donor, isopropyl 2,3,4,6-tetra- O-benzoyl-β- d-galactopyranosyl-(1→6)-[2,3,5-tri- O-benzoyl-α- l-arabinofuranosyl-(1→3)]-2,4-di- O-benzoyl-1-thio-β- d-galactopyranoside, from isopropyl 1-thio-β- d-galactopyranoside using a one-pot synthesis of a 3,6-differentially protected building block.

Chemoenzymatic iterative synthesis of difficult linkages of oligosaccharides on soluble polymeric supports.

[reaction: see text]. A trisaccharide donor containing a cis-Galpalpha(1-->4)Galp linkage was prepared using a synthetic strategy based on chemoenzymatic oligosaccharide synthesis on a soluble polymeric support. Significantly, only retaining glycosyltransferases gave complete reactions, whereas inverting enzymes showed little or no activity with poly(ethylene glycol) (MPEG)-bound lactose as an acceptor. The MPEG-attached trisaccharide was shown to bind to Verotoxin-1 by transfer NOE studies through the Galpalpha(1-->4)Galp portion of the molecule.

Total synthesis of sialylated and sulfated oligosaccharide chains from respiratory mucins.

The total syntheses of several complex oligosaccharide moieties that occur in the core structure of sulfated mucins are reported. A trisaccharide acceptor was obtained through regio- and stereoselective sialylation of methyl (6-O-pivaloyl-beta-D-galactopyanosyl)(1-->3)-4,6-O-benzylidene-2-a cetamido-2-deoxy-alpha-D-galactopyranoside with a novel sialyl donor. A tetrasaccharide, pentasaccharide, and hexasaccharide were constructed in predictable and controlled manner with high regio- and stereoselectivity after the successful preparation and employment of a disaccharide donor, trisaccharide donor, disaccharide acceptor, and trisaccharide acceptor building blocks. Finally, a mild oxidative cleaving method was adopted for the selective removal of 2-naphthylmethyl (NAP) in the presence of benzyl groups.

Synthesis of the β-Methyl Glycoside of Lacto-N-Fucopentaose III

ABSTRACT A total synthesis of the β-methyl glycoside of lacto-N-fucopentaose III (1) is described. Phenyl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-(1→4)-6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (4), a key intermediate prepared by condensation of 2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl bromide (2) and phenyl 6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (3), was glycosylated with ethyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside (5) to give the trisaccharide donor 6, which, on coupling with methyl 2,6-di-O-benzyl-β-D-galactopyranosyl-(1→4) 2,3,6-tri-O-benzyl-β-D-glucopyranoside (7), afforded the pentasaccharide 8. It was easily transformed into the target pentasaccharide 1 via hydrazinolysis, acetylation, O-deacetylation, and hydrogenolysis.

A highly convergent synthesis of the phytoalexin elicitor hexasaccharide

A highly convergent synthesis of the elicitor-active D-glucohexatose 1 and its variant 19 was achieved via coupling of the trisaccharide donor 14 with the trisaccharide acceptor 15 followed by deprotection. 14 and 15 were obtained from rearrangement of the orthoesters 6 and 5 respectively which were prepared quantitatively from coupling of the disaccharide 4 with acetobromoglucose and 6-O-chloroacetylated acetobromoglucose respectively. Graphic

Synthesis and NMR assignment of two repeating units (decasaccharide) of the type III group B Streptococcus capsular polysaccharide and its 13C-labeled and N-propionyl substituted sialic acid analogues

For the purpose of carrying out a comprehensive investigation into the nature of the conformational epitope of the type III group B Streptococcus polysaccharide, combined chemical and enzymatic methods were applied to the synthesis of three decasaccharide probes, namely β-d-Glc-(1 → 6)[ α-NeuR-(2 → 3)- β-d-Gal-(1 → 4)]- β-d-GlcNAc-(1 → 3)- β-d-Gal-(1 → 4)- β-d-Glc-(1 → 6)[ α-NeuR-(2 → 3)- β-d-Gal-(1 → 4)]- β-d-GlcNAc-(1 → 3)- β-d-Gal-OMe ( 22NeuR = NeuAc; 23NeuR = NeuAc with 8% 13C-labeling; 24NeuR = NeuPr). The precursor core octasaccharide 21 was chemically synthesized from trisaccharide donor 11 and pentasaccharide acceptor 19 by block condensation. Sialylation of 21 with α-(2 → 3)-sialyltransferase and CMP-NeuAc afforded 22. In the presence of CMP-sialic acid synthetase and α-(2 → 3)-sialyltransferase, 21 was sialylated with sialic acid derivatives (8% 13C-labeled, or N-propionyl substituted) to give 23 and 24, respectively. Complete assignments of the 1H and 13C NMR spectra of compounds 21, 22 ( 23), and 24 are also presented.

Total synthesis of VIM-2 ganglioside isolated from human chronic myelogenous leukemia cells

A total synthesis of the tumor associated glycolipid antigen, VIM-2, is described [2]. Phenyl 2,3,4- tri-O-benzoyl-6-O-benzyl-β- d-galactopyranosyl-(1 → 4)-6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β- glucopyranoside 7), a key intermediate prepared by condensation of phenyl 6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β- d- glucopyranoside (bd6) and 2,3,4- tri-O-benzoyl-6-O-benzyl-α- d-galacotopyranosyl bromide (bd5), ws glycosylated with methyl 2,3,4-tri-O-benzyl-1-thio-b-1-fucopyranoside (bd8) to give the trisaccharide donor bd9, which on coupling with 2-(trimethysily)ethyl 2,46- tri-O-benzyl-b- d-galactopyranosyl-1-(1 → 4)-2,3->tri-O-benzyl d-glucopyranoside (bd10), afforded the pentasaccharide 11. The regioselective glycosylation of 12 (derived by O-debenzoylation of 11) with 7 gave the heptassacharide 13, which was converted by treatment with hydrazine monohydrate and subsequent N-acetylation into the hexasaccharide acceptor 14. The stereo- and regio-selective glycosilation of 14 with methyl (phenyl 5- acetamido-4,7,8,9-O-benzoyl-3,5-dideoxy-2- thio- d-glycerob- d-galacto-2-nonulopyranosid (bd16) gave the desired octasaccharide 18. Hydrogenolytic removal of the benzyl groups in 18 and successive O-acetylation, removal of the 2-(trimethylsily)ethyl group, and treatment with trichloroacetonitrile gave the α-trichloroacetimidate 21, which was then coupled with (2 S,3 R,4 E)-2-azido-3- O-( tert-butyldiphenysilyl)-4-octadecene-1,3-diol ( 22) to give 23. Compound 23 was transformed, via selective reduction of the azido group, N-introduction of octadecanoic acid, O-desiylation, O-deacylation, and saponification of the metyl ester group, into the titile VIM-2- ganglioside 26.

Glycosyl Imidates, 65. Efficient synthesis of the Lewis antigen X (Lex) family

Abstracttert‐Butyldimethylsilyl 2‐azido‐4,6‐O‐benzylideneglucopyranoside 5 proved to be a versatile starting material for the synthesis of the Lex antigen family. 3‐O‐Fucosylation of 5, ensuing reductive benzylidene ring cleavage, and then 4‐O‐galactosylation afforded Lex trisaccharide building block 12 which was readily converted into trisaccharide donor 14α,β and into trisaccharide 3c‐O‐acceptor 16. Their reaction in acetonitrile as solvent at low temperatures (nitrile effect) afforded exclusively the β‐connected hexasaccharide 17, which was transformed via the same steps into hexasaccharide donor 20α,β and acceptor 22. The use of these building blocks and known lactose derivative 23b, and 3‐O‐benzoylprotected azidosphingosine 32 as acceptors led to ready formation of the target molecules. Thus, from 20α, β and 23b octasaccharide 24b was obtained which was converted via 25b and 26b into O‐unprotected octasaccharide 27; the derived O‐acyl‐protected donor 29bα was linked to 32, thus providing by application of the “azidosphingosine glycosylation procedure” dimeric Lex 1B. From 20α, β and 16 nonasaccharide 35a was obtained; its transformation via 36a and 37a into donor 38aα,β gave by reaction with 23b undecasaccharide 39a; the derived donor 43aα furnished by treatment with 32 trimeric Lex 1C. Similarly, from 20α, β and 22 dodecasaccharide 35b was generated which gave via 36b, 37b, and donor 38bα, β by reaction with 23b as acceptor tetradecasaccharide 39b; 39b, after transformation into the corresponding donor 43bα, β gave by treatment with 32 as acceptor tetrameric Lex 1D. Additionally, octasaccharide donor 29bα, β was attached to spacer 30, thus yielding spacer‐connected dimeric Lex antigen 2. magnified image

Bausteine von Oligosacchariden, CV. Synthese des Pentasaccharids L‐α‐D‐Hep‐(1→3)‐L‐α‐D‐Hep‐(1→5)‐α‐Kdo‐(2→6)‐β‐D‐GlcNhm‐(1→6)‐D‐GlcNhm der linearen Core‐ und Lipoid‐A‐Struktur von Lipopolysacchariden

Building Units of Oligosaccharides, CV. – Synthesis of the Pentasaccharide L‐α‐D‐Hep‐(1→3)‐L‐α‐D‐Hep‐(1→5)‐α‐Kdo‐(2→6)‐β‐D‐GlcNhm‐(1→6)‐D‐GlcNhm of the Linear Core and Lipoid A Structure of LipopolysaccharidesUsing the trichloroacetimidate method we synthesized a trisaccharide donor containing the sequence L‐α‐D‐Hep‐(1→3)‐L‐α‐D‐Hep‐(1→5)‐α‐Kdo. This block was coupled stereoselectively with a lipoid A analogue acceptor 22, composed of two glucosamin units, giving the pentasaccharide 23. After deblocking we obtained the pentasaccharide L‐α‐D‐Hep‐(1→3)‐L‐α‐D‐Hep‐(1→5)‐α‐Kdo‐(2→6)‐β‐D‐GlcNhm‐(1→6)‐D‐GlcNhm (28), which represents the linear structure of the inner core and lipoid A chain of lipopolysaccharides. Sheep erythrocytes can be coated with compound 28 by incorporation of the fatty acids into the cell membrane. This complex presents the antigenic determinant composed of two heptose residues and one Kdo residue above the cell surface.

Synthesis of a pentasaccharide and a heptasaccharide corresponding to an ovarian glycoprotein; studies towards glycosylations

The syntheses of pentasaccharide I and heptasaccharide II, which correspond to an ovarian O-glycoprotein, are presented. The protected pentasaccharide 1 was prepared by condensing a trisaccharide donor 18c with a disaccharide acceptor ( 8b, while condensation of the same trisaccharide donor ( 18c) with a tetrasaccharide acceptor ( 25b) provided the protected heptasaccharide 2. Special attention was paid to the deblocking of the protected derivatives 1 and 2 to give I and II, respectively. The β-bonds in 8b and 25b were prepared by using glycosyl donors with non-participating groups at C-2, which were earlier applied for the synthesis of α-glycosides. For the synthesis of the trisaccharide donor ( 18c), condensations of several activated Galα(1->3)Gal disaccharides with protected GlcNAc residues were compared. It was found that the α/β ratio and the yield of this glycosylation are influenced by the leaving group at the anomeric centre, the character of the participating acyl group and, in particular, by the unfavourable steric interaction between donor and acceptor. In order to reduce this steric interaction between donor and acceptor, the conformation of the GlcNAc acceptor was changed to the 1,6-anhydro derivative 16, which afforded in the glycosylation with glycosyl bromide 13c a high yield of the desired trisaccharide 17.