Synthesis of Tetrasaccharide Repeating Unit of the K-Antigen from Klebsiella Type-16

Abstract

Starting from L-fucose, D-glucose and lactose, methyl O-[2,3-di-O-benzoyl-4, 6-O-(4-methoxybenzylidene)-β-D-glucopyranosyl]-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside and methyl O-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl)-(1→4)-O-(2,3,6-tri-O-benzyl-α-D-glucopyranosyl)-(1→4)-O-(methyl 2,3-di-O-benzoyl-β-D-glucopyranosyluronate)-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside were synthesized. Removal of protecting groups gave the tetrasaccharide repeating unit of the antigen from Klebsiella type-16 in the form of its methyl ester methyl glycoside.     

BLOCK SYNTHESIS WITH GALACTURONATE TRICHLOROACETIMIDATES[1]

The disaccharide methyl (4-O-benzoyl-3-O-benzyl-2-O-acetyl-α-L-rhamno pyranosyl)-(1→4)-(allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate (13) was obtained in an excellent yield of 88% using methyl (allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate ((12) as the glycosyl acceptor and a slight excess of the 1,2-di-O-acetyl-rhamnoglycosyl donor 5a. Disaccharide 13 is a key intermediate that can be used either as a glycosyl acceptor or glycosyl donor for the preparation of rhamnogalacturonan fragments. Here, introduction of the trichloroacetimidate function at the anomeric center gave the disaccharide glycosyl donor 28, which could be applied in a blockwise glycosylation reaction to form the L-Rha-α(1→4)-D-GalA-α(1→4)-D-GalA trisaccharide 29. Generally, on condition that no neighboring group effect influenced the reaction at the anomeric center of the α-trichloroacetimidate galacturonate glycosyl donors (20–22, 28), α-glycosidic linkages were nearly exclusively formed, except in the case of the 4-O-methylgalactopyranosyluronate 22.     

Preparation of trans Diequatorial 2,3-Pyruvate Acetals in a Di- and a Trisaccharide Related to the K-Antigen from E. Coli 0101:K103:H−

Abstract

Using methyl 2,2-bis(ethylthio)propionate as acetalating agent and triflic acid-sulfuryl chloride as catalyst, synthesis of 2,3-trans diequatorial pyruvate ketal was achieved. Starting from D-galactose and L-rhamnose derivatives, methyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl-(1→4)-6-O-benzyl-2,3-O-(1-methoxycarbonyl)ethylidene- α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside and methyl 4,6-di-O-benzyl-2,3-O-(1-methoxy-carbonyl)ethylidene-α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside were synthesized. Removal of the protecting groups from the former, afforded the trisaccharide repeating unit of the K-antigen from E.coli O101:K103:H^? in the form of its methyl glycoside methyl ester.     

Synthesis of a DI- and A Trisaccharide Related to the Antigen From Klebsiella Type 16

Using methyl triflate as promoter, methyl O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-(methyl 2,3-di-O-benzoyl-β-D-glucopyranosyluronate) and methyl O-(2,3,4,6-tetra-O-benzyl-β-D-galacto-pyranosyl)-(1→-4)-O-(2,3,6-tri-O-benzyl-α-D-glucopyranosyl)-1(1→4)-(methyl 2,3-di-O-benzoyl-β-D-glucopyranosyluronate) have been synthesised. Removal of protecting groups gave the di- and trisaccharide in the form of their methyl ester methyl glycoside related to the antigen of Klebsiella type 16.     

Synthesis of a Single Repeat Unit of Type VIII Group B Streptococcus Capsular Polysaccharide 1

Abstract

We have synthesized a single repeat unit of type VIII Group B Streptococcus capsular polysaccharide, the structure of which is {L-Rhap(β1→4)-D-Glcp(β1→4)[Neu5Ac(α2→3)]-D-Galp(β→4)}_n. The synthesis presented three significant synthetic challenges namely: the L-Rhap(β→4)-D-Glcp bond, the Neu5Ac(α2→3)-D-Galp bond and 3,4-D-Galp branching. The L-Rhap bond was constructed in 60% yield (α:β 1:1.2) using 4-O-acetyl-2,3-di-O-benzoyl-α-L-rhamnopyranosyl bromide 6 as donor, silver silicate as promotor and 6-O-benzyl-2,3-di-O-benzoyl-1-thio-β-D-glucopyranoside as acceptor to yield disaccharide 18. The Neu5Ac(α2→3) linkage was synthesized in 66% yield using methyl [phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-nonulopyranosid]onate as donor and triol 2-(trimethylsilyl) ethyl 6-O-benzyl-β-D-galactopyranoside as acceptor to give disaccharide 21. The 3,4-D-Galp branching was achieved by regioselective glycosylation of disaccharide diol 21 by disaccharide 18 in 28% yield to give protected tetrasaccharide 22. Tetrasaccharide 22 was deprotected to give as its 2-(trimethylsilyl)ethyl glycoside the title compound 1a. In addition the 2-(trimethylsilyl)ethyl group was cleaved and the tetrasaccharide coupled by glycosylation (via tetrasaccharide trichloroacetimidate) to a linker suitable for conjugation.

     

Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

The stereocontrolled synthesis of methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (EC, 1), methyl α-L-rhamnopyranosyl-(1→3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (B(E)C, 3) and methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyl-α-L-rhamnopyranoside (11) and 8 afforded the fully protected αE-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding βE-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding βE-disaccharide, namely, methyl β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (βEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the αE and βE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required αE-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.     

Linear Synthesis of The Methyl Glycosides of Tri-, Tetra-, and Pentasaccharide Fragments of The Shigella Flexneri Serotype 5A O-Antigen

ABSTRACT

The stepwise synthesis of methyl α-D-glucopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (EBC-OMe, 1), methyl α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (A(E)BC-OMe, 2), and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (DA(E)BC-OMe, 3) is described. Compounds 1, 2 and 3 constitute the methyl glycosides of fragments of the O-specific polysaccharide of Shigella flexneri serotype 5a. Methyl 2,4-di-O-benzoyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzoyl-α-L-rhamnopyranoside was an appropriate BC precursor for the synthesis of 1. For the synthesis of the branched targets 2 and 3, a benzyl group was best suited at position 2 of rhamnose C. Thus, methyl 4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside was the key intermediate to the BC portion. In all cases, 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride was a convenient E precursor, when used in combination with titanium tetrafluoride. All along, attention was paid to steric hindrance as a factor of major impact on the condensation steps outcome. Therefore, based on previous experience, 2-O-acetyl-3,4-di-O-allyl-α-L-rhamnopyranosyl trichloroacetimidate and 3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-α-D-glucopyranosyl trichloroacetimidate were used as donors. Both suited all requirements when used as key precursors for residues A and D in the synthesis of 3, respectively.     

Synthesis of Four Spacer-Containing Trisaccharides with the 4-0-(β-L-Rhamnopyranosyl)-D-glucopyranose Unit in Common,Representing Fragments of Capsular Polysaccharides from Streptococcus Pneumoniae Types 2, 7F, 22F,and 23F

Abstract

The synthesis is reported of 3-aminopropyl 3-O-[4-O(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-α-L-rhamnopyranoside (34), 3-aminopropyl 2-acetamido-3-O-[4-0-(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-2-deoxy-β-D-galactopyranoside (37), 3-aminopropyl 3-O-[4-O-(β-L-rhamnopyranosyl)-α-D-glucopyranosyl]-α-D-galactofuranoside (41), and 3-aminopropyl 4-O-[4-O-(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-galactopyranoside (45). These are spacer-containing fragments of the capsular polysaccharides of Streptococcus pneumoniae type 2, 7F, 22F, and 23F, respectively, which are constituents of Pneumovax^© 23. 2,3,4-Tri-O-benzyl-α-L-rhamnopyranosyl bromide was coupled to l,6-anhydro-2,3-di-(O-benzyl-β-D-glucopyranose (3). Opening of the anhydro ring, removal of AcO-1, and imidation of l,6-anhydro-2,3-di- O-benzyl-4-O-(2,3,4-tri-O-benzyl-β-L-rhamnopyranosyl)-β-D-glucopyranose (4β) afforded 6-O-acetyl-2,3-di-O-ben-zyl-4-O-(2,3,4-tri- O-benzyl-β-L-rhamnopyranosyl)-αβ-D-glucopyranosyl trichloroacet-imidate (7αβ). Condensation of 7αβ with 3-N-benzyloxycarbonylaminopropyl 2-O-ben-zyl-5,6-O-isopropylidene-α-D-galactofuranoside (26), followed by deprotection gave 41 Opening of the anhydro ring of 4 p followed by debenzylation, acerylauon, removal of AcO-1, and imidation yielded 2,3,6-tri-(9-aceryl-4-O-(2,3,4-tri-0-acetyl-P-L-rharnnopyran-.-osyl)-α-D-glucopyranosyl trichloroacetimidate (11). Condensation of 11 with 3-N-bcn-zyloxycarbonylaminopropyl 2,4-di-O-benzyl-α-L-rhamnopyranoside (18), with 3-N-bcn-zyloxycarbonylaminopropyl 2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-galactopyran-oside (21), or with 3-N -benzyloxycarbonylaminopropyl 2-O-acetyl-3-O-allyl-6-O-benzyl-β-D-galactopyranoside (31), followed by deprotection afforded 34, 37, and 45, respectively.     

Synthetic Studies on Sialoglycoconjugates 90: Total Synthesis of Sulfated Glucuronyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl paragloboside derivatives (pentasaccharides) have been synthesized. The important intermediate designed for a facile sulfation in the last step and effective, stereocontrolled glycosidation, methyl (4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-α-D-glucopyranosyl trichloroacetimidate)uronate (8) was prepared from methyl [2-(trimethylsilyl)ethyl β-D-glucopyranosid]uronate (3) via selective 4-O-acetylation, 2-O-benzoylation, 3-O-levulinoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation. The glycosylation of 8 with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (9) using trimethylsilyl trifluoromethanesulfonate gave 2-(trimethylsilyl)ethyl O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (10), which was transformed via removal of the benzyl group, benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the disaccharide donor 13. On the other hand, 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (20) as the acceptor was prepared from 2-(trimethylsilyl)ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside (14) via O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with 2-(trimethylsilyl)ethyl O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (18), removal of the O-acetyl and N-phthaloyl group followed by N-acetylation. Condensation of 13 with 20 using trimethylsilyl trifluoromethanesulfonate afforded the desired pentasaccharide 21, which was transformed by removal of the benzyl group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the pentasaccharide donor 24. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25) with 24 gave the desired β-glycoside 26, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.     

Preparation of Primary and Secondary Azidosugars from Diols using the Dioxaphosphorane Methodology

ABSTRACT

Treatment of methyl 2,3-di-O-benzyl-α-D-glucopyranoside (1), methyl 2,3-di-O-acetyl-α-D-glucopyranoside (4), 3-O-benzyl-1,2-O-(1-methylethylidene)-α-D-glucofuranose (6), 3-O-acetyl-1,2-O-(1-methylethylidene)-α-D-glucofuranose (9), 1,2-O-(1-methylethylidene)-α-D-xylofuranose (11) and methyl 2,3-di-O-acetyl-α-D-galactopyranoside (15) with diisopropylazodicarboxylate-triphenylphosphine in tetrahydrofuran led to the corresponding dioxaphosphoranes, which were opened by trimethylsilyl azide affording the silylated primary azidodeoxysugars. When the same reaction was performed on methyl 2,3-di-O-benzyl-α-D-galactopyranoside (20), an inversion of the regioselectivity of the dioxaphosphorane opening was observed, leading mainly to the 4-azido-4-deoxy-α-D-glucopyranoside derivative 27.     

Preparation of 2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-β-D-allopyranose and Its Disaccharide Derivative

Abstract

2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-D-allopyranose, needed as one of the building blocks for construction of a novel cyclodextrin-like compound, was prepared in the form of crystalline β-anomer 6 from methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-allopyranoside 1. As a model of α-glycosidation necessary for formation of a cyclic structure, 6 was converted into the corresponding β-glycosyl trichloroacetimidate and coupled with methyl 6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside 8, giving α(1→4)-linked disaccharide derivative 9.     

Talopyranose Derivatives Suitable for the Planned Synthesis of Teichoic Acids Containing Di-Glycosylated Ribitol Units

ABSTRACT

Easily accessible 1,6-anhydro-2,3-O-(S)-benzylidene-β-D-mannopyranose was converted in four steps to 1,6-anhydro-3,4-di-O-benzyl-β-D-talopyranose. Glycosylation of the latter with ethyl 2,3,4-tri-O-acetyl-1-thio-α-L-rhamnopyranoside gave, after further processing, 1-O-allyl-3,4-di-O-benzyl-2-O-(2,3,4-tri-O-benzyl-α-L-rhamnopyranosyl)-L-ribitol.     

Synthesis of a Tri- and Tetrasaccharide Fragment Specific for the Shigella flexneri Serotype 5a O-Antigen. A Reinvestigation

ABSTRACT

Stereocontrolled, stepwise synthesis of methyl α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside (A(E)B, 1) and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside (DA(E)B, 2) is described; these constitute the methyl glycosides of fragments of the O-specific polysaccharide of Shigella flexneri serotype 5a. Two routes to trisaccharide 1 were considered. Route 1 involved the coupling of a precursor to residue A and a disaccharide EB, whereas route 2 was based on the condensation of a precursor to residue E and a disaccharide AB. Rather surprisingly, the latter afforded the β-anomer of 1, namely methyl α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside as the major product. Route 1 was preferred. Overall, several observations made during this study suggested that, for the construction of higher fragments, a suitable precursor to rhamnose A would require protecting groups of low bulkiness at position 3 and 4. Therefore, the 2-O-acetyl-3,4-di-O-allyl-α-L-rhamnopyranosyl trichloroacetimidate (35) was the precursor of choice to residue A in the synthesis of the tetrasaccharide 2. The condensation product of 35 and methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-4-O-benzyl-α-L-rhamnopyranoside was selectively deacylated and condensed to 2-trichloroacetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl trichloroacetimidate to afford the corresponding fully protected tetrasaccharide 45. Controlled stepwise deprotection of the latter proceeded smoothly to afford the target 2. It should be emphasised that the preparation of 45 was not straightforward, several donors and coupling conditions that were tested resulted only in the complete recovery of the acceptor. Distortion of several signals in the ¹³C NMR spectra of the fully or partially protected tetrasaccharide intermediates suggested that steric hindrance, added to the known low reactivity of HO-2 of rhamnosyl acceptors, probably played a major role in the outcome of the glycosidation attempts.     

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 2_B and/or 2_A of key tri- and tetrasaccharide intermediates bearing a protecting group at position 2_C 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.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes. II. the Synthesis of the 4- and 4′″-Monodeoxygenated Analogues

ABSTRACT

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at positions 4 or 4′″ have been synthesized in [2+2] block syntheses. After the preparation of precursors with only one free hydroxyl group the deoxy function was introduced by a Barton-McCombie reaction. Thus, glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (4) with octa-O-acetyl-β-maltose (3) gave tetrasaccharide 5 with only one free hydroxyl group at the 4-position. The 4′-position of an allyl maltoside was available selectively after removal of a 4′,6′-cyclic acetal and selective benzoylation of the 6′-position. Reduction of this derivative 11 afforded allyl O-(2,3-di-O-acetyl-6-O-benzoyl-4-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranoside (14), which was deallylated, activated as an trichloroacetimidate, and coupled to 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (20). Several compounds were fully characterized by ¹H NMR spectroscopy. Deprotection furnished the monodeoxygenated tetrasaccharides 9 and 23.     

Synthetic Antigens: Synthesis of 4-Aminophenyl O-α-D-Mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→6)-O-α-D-Mannopyranoside and A Related Di- and A Trisaccharide

Abstract

4-Nitrophenyl 2,3-O-isopropylidine-α-D-mannopyranoside 2 was condensed with O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-(1→2)-3,4,6-tri-O-acetyl-α-D-mannopyranosyl bromide 1 and 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl bromide 11 in the presence of mercuric cyanide. Products were deprotected to yield, respectively, 4-nitrophenyl O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 6 and 4-nitrophenyl O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 14. The 4-nitrophenyl group of 6 was reduced to give title trisaccharide. Bromide 1 was also condensed with methyl 2,3,4-tri-O-benzyl-α-D-manopyranoside 3 in the presence of silver trifluoromethanesulfonate and tetramethylurea to give protected trisaccharide derivative which was deprotected to furnish, methyl O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 10. The identities of all protected and deprotected compounds were supported by ¹H and ¹³C NMR spectral data.     

Synthetic Studies on Sialoglycoconjugates 89: Synthesis of Ganglioside GM3 and KDN-GM3 Containing Different Carbon-Chain Length Fatty Acyl Groups at the Ceramide Residue

ABSTRACT

Ganglioside GM₃ and KDN-ganglioside GM₃, containing hexanoyl, decanoyl, and hexadecanoyl groups at the ceramide moiety have been synthesized. Selective reduction of the azido group in O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (1) and O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (2), coupling with hexanoic, decanoic, and hexadecanoic acids, O-deacylation, and de-esterification gave the title gangliosides GM₃ (11→13) and KDN-GM₃ (14→16) in good yields. On the other hand, O-deacylation of 1 and subsequent de-esterification gave 2-azido-sphingosine containing-GM₃ analogue 17, which was converted into lyso-GM₃, in which no fatty acyl group was substituted at the sphingosine residue, by selective reduction of the azido group.     

Synthetic Studies on Sialoglycoconjugates 70: Synthesis of Sialyl and Sulfo Lewis × Analogs Containing a Ceramide or 2-(Tetradecyl)hexadecyl Residue

Abstract

Four sialyl and sulfo Le^x analogs containing glucose in place of N-acetylglucosamine, and a ceramide or 2-(tetradecyl)hexadecyl residue, have been synthesized. Condensation of O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-O-(4-O-acetyl-2,6-diO-benzoyl-β-d-galactopyranosyl)-(1→4)-O-[(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)-(1→3)]-2,4-di-O-benzoyl-α-d-glucopyranosyl trichloroacetimidate (1) with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3, diol (2) or 2-(tetradecyl)-hexadecyl-1-ol (3) gave the corresponding β-glycosides 4 and 7. Compound 4 was converted into the ganglioside 6 via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and saponification of the methyl ester group. Hydrolysis of the O-acyl groups in 7 followed by saponification of the methyl ester, gave sialyl Le^x ganglioside analog 8 containing a branched fatty alkyl residue. On the other hand, glycosylation of O-(4-O-acetyl-2,6-di-O-benzoyl-3-O-levulinyl-β-d-galactopyranosyl)-(1→4)-[O-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)-(1→3)]-2,6-di-O-benzoyl-α-d-glucopyranosyl trichloroacetimidate (13), prepared from 2-(trimethylsilyl)ethyl O-(2,6-di-O-benzoyl-β-d-galactopyranosyl)-(1→4)-O-[(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)]-2,6-di-O-benzoyl-β-d-glucopyranoside (9) via selective 3-O-levulinylation, acetylation, removal of the 2-(trimethylsilyl)ethyl group, with 2 or 3, gave the desired β-glycosides 14 and 19. Selective reduction of the axido group in 14 followed by coupling with octadecanoic acid gave the ceramide derivative 16. Removal of the levulinyl group in 16 and 19, treatment with sulfur trioxide pyridine complex and subsequent hydrolysis of the protecting groups yielded the corresponding sulfo Le^x analogs 18 and 21.     

Synthetic Studies on Sialoglycoconjugates 54: Synthesis of I-Active Ganglioside Analog

Abstract

A stereocontrolled synthesis of I-active ganglioside analog is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-O-benzyl-4,6-O-benzylidene-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) with methyl 4-O-acetyl-1,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (10) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) gave the desired trisaccharide 11, which was transformed into trisaccharide acceptor 14 via removal of the phthaloyl group followed by N-acetylation, and debenzylidenation. Glycosylation of 14 with methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (8) gave the biantennary compound 15, which was transformed into the acceptor 16. Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 16 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (17) afforded the desired hexasaccharide 19. Coupling of the hexasaccharide acceptor 20, prepared from 19 by reductive ring-opening of benzylidene acetal, with 17 gave octasaccharide derivative 21. Compound 21 was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor 24. Condensation of 24 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside 25, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound 28.     

Synthetic Studies on Sialoglycoconjugates 104: Synthesis of Kdn-Lewis X Ganglioside Analogs Containing Modified Reducing Terminal and L-Rhamnose in Place of L-Fucose 1 2

Abstract

KDN-Le^x ganglioside analogs (10, 13, 16 and 19) containing the modified reducing terminal and L-rhamnose in place of L-fucose have been synthesized. Glycosidation of methyl 2,3,4-tri-O-benzyl-1-thio-α-L-rhamnopyranoside (1) with 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-α-D-galacopyranoside (2), followed by reductive ring opening of the benzylidene acetal, gave 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-α-L-rhamnopyranosyl)-(1→3)-O-(2-acet-amido-6-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (4). The tetrasaccharide 4 was coupled with methyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-galactopyranoside(5), using dimethyl(methylthio)sulfonium triflate (DMTST), to give the hexasaccharide 6, which was converted into compound 11 in the usual manner. Compounds 8 and 11 were transformed, via bromination of the reducing terminal, radical reduction, O-deacylation and saponification of the methyl ester, into the desired KDN-Le^x hexasaccharides (10, 13). On the other hand, glycosylation of 2-(tetradecyl)hexadecanol with α-trichloroacetimidates 14 and 17, afforded the target ganglioside analogs 16 and 19.