Target Tetrasaccharide Research Articles

Synthesis of a tetrasaccharide corresponding to the teichoic acid from the cell wall of Streptomyces sp. VKM Ac-2275

A concise chemical synthesis of a tetrasaccharide found in the teichoic acid from the cell wall of Streptomyces sp. VKM Ac-2275 was achieved in high yield. A [2+2] block synthetic strategy has been adopted for the construction of the target tetrasaccharide by exploiting the orthogonal property of a thioglycoside. For the first time, the 2-(4-methoxyphenoxy) ethyl group has been used as the anomeric protecting group to make the glycone moiety with a readily available linker for its conjugation to a protein without destroying the cyclic structure at the reducing end. Yields were high in all of the intermediate steps.

Total synthesis of a unique tetrasaccharide present in the human clotting factor IX and mammalian Notch 1 receptor

The synthesis of a unique tetrasaccharide linked to the serine 61 of human clotting factor IX through an α- l-fucose residue has been achieved for the first time in excellent yield. All glycosylation and protecting group manipulation steps are high yielding and reproducible for a scale-up preparation. A sequential glycosylation strategy has been used to assemble suitably protected monosaccharide synthons for the preparation of the target tetrasaccharide.

Synthesis of the 6-deoxytalose-containing tetrasaccharide of the glycopeptidolipid from Mycobacterium intracellare serotype 7

An efficient synthesis of 4-methoxyphenyl α- l-Rha p-(1→3)-α- l-Rha p-(1→3)-α- l-Rha p-(1→2)-6-deoxy-α- l-Tal p, the tetrasaccharide related to the GPLs of Mycobacterium intracellare serotype 7, was achieved with 4-methoxyphenyl 3,4-di- O-benzoyl-6-deoxy-α- l-talopyranoside ( 6c) as the key intermediate which was obtained through selective 3-O-benzoylation of 4- O-benzoyl-6-deoxy-α- l-taloside. Coupling of 6c with 3- O-allyloxycarbonyl-2,4-di- O-benzoyl-α- l-rhamnopyranosyl trichloroacetimidate followed by removal of the allyloxycarbonyl protecting group afforded the disaccharide acceptor 11. Condensation of 11 with 2,3,4-tri- O-benzoyl-α- l-rhamnopyranosyl-(1→3)-2,4-di- O-benzoyl-α- l-rhamnopyranosyl trichloroacetimidate and subsequent deprotection gave the target tetrasaccharide.

Synthesis of the tetrasaccharide α- d-Glc p-(1→3)-α- d-Man p-(1→2)-α- d-Man p-(1→2)-α- d-Man p recognized by Calreticulin/Calnexin

The title compound as its methyl glycoside was efficiently synthesized using a block synthesis approach. Halide-assisted glycosidations between 6- O-acetyl-2,3,4-tri- O-benzyl-α- d-glucopyranosyl iodide and ethyl 2- O-acetyl-4,6-di- O-benzyl-1-thio-α- d-mannopyranoside using triphenylphosphine oxide as promoter yielded, with complete α-selectivity, a disaccharide building block in high yield. The perbenzylated derivative of this proved to be an excellent donor affording 88% of the protected target tetrasaccharide in an NIS/AgOTf-promoted coupling to a known methyl dimannoside acceptor. Deprotection through catalytic hydrogenolysis then gave the target compound in 47% overall yield.

First synthesis of the immunodominant β-galactofuranose-containing tetrasaccharide present in the cell wall of Aspergillus fumigatus

β-Gal f-(1→5)-β-Gal f-(1→6)-α-Man p-(1→6)-α-Man p, the immunodominant epitope in the cell-wall galactomannan of Aspergillus fumigatus, was synthesized for the first time as its allyl glycoside. The key disaccharide glycosyl donor, 2,3,5,6-tetra- O-benzoyl-β- d-galactofuranosyl-(1→5)-2- O-acetyl-3,6-di- O-benzoyl-β- d-galactofuranosyl trichloroacetimidate ( 10), was constructed by 5- O-glycosylation of 1,2- O-isopropylidene-3,6-di- O-benzoyl-α- d-galactofuranose ( 4) with 2,3,5,6-tetra- O-benzoyl-β- d-galactofuranosyl trichloroacetimidate ( 5), followed by 1,2- O-deacetonation, acetylation, selective 1- O-deacetylation, and trichloroacetimidation. The target tetrasaccharide 16 was obtained by the condensation of allyl 2,3,4-tri- O-benzoyl-α- d-mannopyranosyl-(1→6)-2,3,4-tri- O-benzoyl-α- d-mannopyranoside ( 14) as glycosyl acceptor with the disaccharide glycosyl donor 10, followed by deprotection.

Total Synthesis of the Glc3Man N‐Glycan Tetrasaccharide.

Abstract The total synthesis of the tetrasaccharide Glcα(1→2)Glcα(1→3)Glcα(1→3)ManαOMe, which corresponds to the terminal tetrasaccharide portion of the glucose terminated arm of the N-glycan tetradecasaccharide, was achieved by the use of differentially protected selenoglycosides and thioglycosides as glycosyl donors, all of which possessed non-participating protection of the 2-hydroxyl group. Favourable anomeric stereoselectivity was achieved for the glycosylation reactions by the use of ether as solvent, or co-solvent. Global deprotection by catalytic hydrogenation with palladium acetate in a mixture of ethanol and acetic acid yielded the target tetrasaccharide.

Total synthesis of the Glc 3Man N-glycan tetrasaccharide

The total synthesis of the tetrasaccharide Glcα(1→2)Glcα(1→3)Glcα(1→3)ManαOMe, which corresponds to the terminal tetrasaccharide portion of the glucose terminated arm of the N-glycan tetradecasaccharide, was achieved by the use of differentially protected selenoglycosides and thioglycosides as glycosyl donors, all of which possessed non-participating protection of the 2-hydroxyl group. Favourable anomeric stereoselectivity was achieved for the glycosylation reactions by the use of ether as solvent, or co-solvent. Global deprotection by catalytic hydrogenation with palladium acetate in a mixture of ethanol and acetic acid yielded the target tetrasaccharide.

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.

Linear Synthesis of the Methyl Glycosides of Tetra- and Pentasaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT Starting from the known methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2-O-benzoyl-α-L-rhamnopyranoside, the stepwise linear syntheses of methyl α-L-rhamnopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→ 3)-[α-D-glucopyranosyl-(1→ 4)]-α-L-rhamnopyranoside (AB(E)C, 4), and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→ 2)-α-L-rhamnopyranosyl-(1→ 3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (DAB(E)C, 5) are described; these constitute the methyl glycosides of a branched tetra- and pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a, respectively. The chemoselective O-deacetylation at position 2B and/or 2A of key tri- and tetrasaccharide intermediates bearing a protecting group at position 2C was a limiting factor. As such a step occurred once in the synthesis of 4 and twice in the synthesis of 5, the regioselective introduction of residue A on a B(E)C diol precursor (12) and that of residue D on an AB(E)C diol precursor (19) was also attempted. In all cases, a trichloroacetimidate donor was involved. The latter pathway was found satisfactory for the construction of the target 4 using the appropriate tri-O-benzoyl rhamnosyl donor. However, attempted chain elongation of 12 using 2-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranosyl trichloroacetimidate (8) resulted in an inseparable mixture which needed to be benzoylated to allow the isolation of the target tetrasaccharide. Besides, condensation of the corresponding tetrasaccharide acceptor and the N-acetylglucosaminyl donor was sluggish. As the target pentasaccharide was isolated in a poor yield, this route was abandoned.

The Synthesis of Four Dideoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Four derivatives of β-maltosyl-(1→4)-trehalose were prepared, each with two deoxy functions in one of the constitutive disaccharide building blocks. 2,3-Di-O-acetyl-4,6-dideoxy-4,6-diiodo-α-D-galactopyranosyl- (1→4) −1,2,3,6-tetra-O-acetyl-D-glucopyranose (3) was employed as a precursor for the 4‴,6‴-dideoxygenated tetrasaccharide 9: coupling of 3 with 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzylidene-α-D-glucopyranoside (4) furnished the tetrasaccharide 5 which was deiodinated and deprotected to yield the target tetrasaccharide 9. Secondly, the dideoxygenated maltose derivative 3-deoxy-4,6-O-isopropylidene-2-O-pivaloyl-β-D-glucopyranosyl- (1→4) −1,6-anhydro-3-deoxy-2-O-pivaloyl-β-D-glucopyranose (10) was ring-opened to the anomeric acetate 11. A [2+2] block synthesis with 4 in TMS triflate mediated glycosylation gave a tetrasaccharide which was deprotected to the 3″,3‴-dideoxygenated analogue of β-maltosyl-(1→4)-trehalose. For the third tetrasaccharide, 2,3,2″,3′-tetra-O-benzyl-α,α-trehalose was iodinated at the primary positions and deiodinated in the presence of palladium-on-carbon, then this acceptor was selectively glycosylated with hepta-O-acetyl-maltosyl bromide (20). Removal of protective groups furnished the maltosyl trehalose tetrasaccharide deoxygenated at positions C-6 and C-6′. to prepare a 3,3′-dideoxygenated trehalose, the free hydroxyl groups of 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranosyl 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranoside (25) were reduced by Barton-McCombie deoxygenation. One of the benzylidene groups was opened reductively with sodium cyanoborohydride. The resulting free hydroxyl group at the 4′-position was glycosylated in a Koenigs-Knorr reaction with 20 to yield the 3,3′-dideoxygenated tetrasaccharide 32, the fourth target oligosaccharide, after deprotection.

Synthetic Studies on Sialoglycoconjugates 95: Total Synthesis of Sulfated Glucuronyl Lactosaminyl Paraglobosides

ABSTRACT 3-O-Sulfo glucuronyl neolactohexanosyl ceramide derivatives (heptasaccharides) have been synthesized. Condensation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl trichloroacetimidate (1) gave the desired β-glycoside 3, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (4) via removal of the O-acetyl and N-phthaloyl groups, followed by N-acetylation. Glycosylation of 4 with O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (5) using trimethylsilyl trifluoromethanesulfonate gave the target tetrasaccharide 6, which was transformed via removal of the benzyl group, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the tetrasaccharide donor 9. Glycosylation of 2-(trimethylsi...

Glycosyl Imidates, 66. Synthesis of the Tetrasaccharide Moiety of Plant Growth Regulator Calonyctin A

Abstract3‐O‐Benzyl‐protected quinovose 6 was transformed into 1,2‐O‐unprotected derivative 9 which on treatment with TBS‐Cl in the presence of a base gave selectively 2‐O‐unprotected glycosyl acceptor 10. Similarly, 3‐O‐allyl‐protected quinovose 11 was transformed into 1,2‐O‐unprotected derivative 14. 1,2‐O‐Acetylation of 14, selective removal of the 1‐O‐acetyl group with hydrazinium acetate, and subsequent treatment with trichloroacetonitrile in the presence of DBU furnished the versatile 2‐O‐acetyl‐3‐O‐allyl‐protected quinovosyl donor 17. Reaction of donor 17 with acceptor 10 in the presence of TMSOTf as the catalyst gave disaccharide 19. Treatment of 19 with NaOMe/MeOH provided 2b‐O‐unprotected derivative 20 which gave with rhamnosyl donor 18 in the presence of TMSOTf as the catalyst trisaccharide 21. 3b‐O‐Deallylation of 21 and subsequent reaction with donor 17, again in the presence of TMSOTf as the catalyst, gave target tetrasaccharide 2. Removal of all O‐protective groups furnished D‐Quiß(1→3)[L‐Rhaα(1→2)]D‐Quiß(1→2)D‐Qui (3), the tetrasaccharide moiety of calonyctin A. magnified image