Synthesis of the isomeric trisaccharides, methyl O-alpha-L-fucopyranosyl- (1----3, 4, and 6)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-beta- D-galactopyranoside

Benzylation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D- glucopyranosyl)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside with benzyl bromide in N,N-dimethylformamide in the presence of sodium hydride afforded methyl 3-O- (2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl) -2,4,6- tri-O-benzyl-beta-D-galactopyranoside (3). Reductive ring-opening of the benzylidene group of 3 gave methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D- glucopyranosyl)- 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (4). Cleavage of the 4,6-acetal group of 3 with hot, 80% aqueous acetic acid afforded the diol (5). Compounds 3, 4, and 5 were each subjected to halide ion-catalyzed glycosylation with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide to produce the corresponding trisaccharide derivatives, which, on catalytic hydrogenation, furnished the title trisaccharides, respectively.     

Synthesis of propyl and 2-aminoethyl glycosides of alpha-D-galactosyl-(1-->3')-beta-lactoside.

Propyl and 2-aminoethyl alpha-D-galactopyranosyl-(1-->3')-beta-lactosides (1 and 2) were prepared from the corresponding perbenzylated trisaccharide allyl glycoside 6 which, in turn, was obtained by methyl triflate promoted alpha-galactosylation of benzylated allyl lactoside acceptor 4 with thiogalactoside 3. Transformation of the allyl moiety in compound 6 into 2-azidoethyl one was achieved by cleavage of the double bond followed by reduction into alcohol 9, subsequent mesylation, and mesylate-->azide substitution. Alternatively trisaccharide 2 was synthesized using alpha-galactosylation of selectively benzoylated 2-azidoethyl lactoside 19 with 3 as the key step.     

Synthetic mucin fragments: methyl 3-O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl-beta-D- 3-O-(2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl- beta-D-glucopyranosyl)-beta-D-galactoyranoside. pyranosyl)-beta-D-galactopyranoside

Methyl 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (5) was obtained crystalline by way of its 3-O-allyl derivative, which was in turn obtained by ring-opening of a presumed 3,4-O-stannylene derivative of methyl beta-D-galactopyranoside, followed by benzylation. Condensation of 5 with 2-methyl-(2-acetamido-3,4,6-tri-O-acetyl-1,2-dideoxy-beta-D-glucopyra no)-[2,1-d]-2-oxazoline in 1,2-dichloroethane in the presence of p-toluenesulfonic acid afforded the disaccharide derivative methyl 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2, 4,6-tri-O-benzyl-beta-D-galactopyranoside (6) Deacetylation of 6 in methanolic sodium methoxide afforded the disaccharide derivative 7, which was acetalated with alpha, alpha-dimethoxytoluene to afford the 4',6'-O-benzylidene acetal (10). Catalytic hydrogenolysis of the benzyl groups of 7 afforded the title disaccharide 8. Glycosylation of 10 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of mercuric cyanide gave the fully protected trisaccharide derivative 12. Systematic removal of the protecting groups of 12 then furnished the title trisaccharide 14. The structures of 5, 8, and 14 were all confirmed by 13C-n.m.r. spectroscopy. The 13C-n.m.r. chemical shifts for methyl alpha- and beta-D-galactopyranoside, and also those of their 3-O-allyl derivatives, are recorded, for the sake of comparison, in conjunction with those of compound 5.     

Synthesis of a hexasaccharide,the repeating unit of O-deacetylated GXM of C. neoformans serotype A

beta-D-GlcpA-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)[-beta-D-Xylp-(1-->2)]-alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A, was synthesized as its allyl glycoside. Thus, 3-O-selective acetylation of allyl 4,6-O-benzylidene-alpha-D-mannopyranoside afforded 2, and subsequent glycosylation of 2 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate furnished the beta-(1-->2)-linked disaccharide 4. Debenzylidenation followed by benzoylation gave allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-3-O-acetyl-4,6-di-O-benzoyl-alpha-D-mannopyranoside (5), and selective 3-O-deacetylation gave the disaccharide acceptor 6. Coupling of 6 with 2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate yielded the trisaccharide 8, and subsequent deallylation and trichloroacetimidation gave 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-[2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)]-4,6-di-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (9). Condensation of the trisaccharide donor 9 with the disaccharide acceptor 6 gave the pentasaccharide 10 whose 2-O-deacetylation gave the acceptor 11. Glycosylation of 11 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate trichloroacetimidate and subsequent deprotection gave the target hexasaccharide.     

The allyl group for protection in carbohydrate chemistry. 17. Synthesis of propyl O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3- di-O-methyl-alpha-L-rhamnopyranosyl)-(1----2)-3-O-methyl-alpha- L-rhamnopyranoside: the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae

Allyl 4-O-benzyl-alpha-L-rhamnopyranoside was converted into allyl 4-O-benzyl-3-O-methyl-alpha-L-rhamnopyranoside and this was condensed with 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl chloride to give a disaccharide derivative which was converted into allyl 4-O-benzyl-2-O-(2,3-O-isopropylidene-alpha-L-rhamnopyranosyl)-3-O-methyl -alpha- L-rhamnopyranoside. This disaccharide derivative was condensed with 2,4-di-O-acetyl-3,6-di-O-methyl-alpha-D-glucopyranosyl chloride to give a trisaccharide derivative which was converted into the title compound. This compound represents the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae which is required to prepare a synthetic diagnostic agent for leprosy infection at an early stage and to investigate the specificities of monoclonal antibodies directed towards the glycolipid.     

Synthesis of 3-O-sulfoglucuronyl lacto-N-neotetraose 2-aminoethyl glycoside and biotinylated neoglycoconjugates thereof

The 2-aminoethyl glycoside of pentasaccharide 3-O-sulfo-GlcA(beta-1-->3)Gal(beta-1-->4)GlcNAc(beta-1-->3)Gal(beta-1--> 4)Glc(beta (1) and its conjugates with biotin and biotinylated polyacrylic acid were synthesized as molecular probes to investigate the recognition of the HNK-1 epitope containing carbohydrates by proteins. Key steps in the first of two investigated schemes for the preparation of the target compound 1 were (a) assembling of the pentasaccharide backbone (compound 10) by glycosylation of selectively substituted allyl glycoside of the trisaccharide GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta with glucuronyl-galactose glycosyl donor, (b) transformation of the allyl aglycon in 10 into 2-azidoethyl one (to give 11), (c) selective deprotection of the OH group at C-3 of the GlcA residue in 11 via saponification, intramolecular formation of 6,3-lacton (13) and its methanolysis, and (d) subsequent O-sulfation. The alternative scheme with the use of 2-azido-ethyl glycoside of the trisaccharide GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta instead of the allyl glycoside 6 was less effective due to smaller yield at the step of pentasaccharide synthesis. Additionally to 1 the 2-aminoethyl glycosides of the oligosaccharides GlcA(beta-1-->3)Gal(beta-1-->4)GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta, 3-O-sulfo-GlcA(beta-1-->3)Gal(beta, and GlcA(beta-1-->3)Gal(beta were also synthesized.     

Synthesis of a 6(V)-sulfated mannopentasaccharide analogue related to PI-88

An efficient and convergent synthesis of a regioselectively 6(V)-sulfated mannopentasaccharide derivative 1c, octyl 6-O-sulfo-alpha-D-mannopyranosyl-(1-->3)-alpha-D-mannopyranosyl-(1-->3)-alpha-d-mannopyranosyl-(1-->3)-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranoside, was achieved by a '3 + 2' strategy. The target was designed to mimic the promising anticancer agent PI-88 and was obtained from the building blocks, octyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside, allyl 2,4,6-tri-O-benzoyl-3-O-(4-methoxybenzyl)-alpha-D-mannopyranoside, and 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (11), under TMSOTf-catalyzed glycosylation conditions. Compound 1c displays a mild anti-angiogenic activity based on a chorioallantoic membrane (CAM) model study.     

Synthesis of neoglycoproteins containing D-glycero-D-talo-oct-2-ulopyranosylonic acid (Ko) ligands corresponding to core units from Burkholderia and Acinetobacter lipopolysaccharide

Glycal esters of Kdo derivatives were converted into 2,3-anhydro intermediates, which were transformed into D-glycero-D-talo-oct-2-ulopyranosylonic acid (Ko), as well as 3-O- and 4-O-p-nitrobenzoyl-Ko derivatives. The exo-allyl orthoester derivative, methyl [5,7,8-tri-O-acetyl-4-O-(4-nitrobenzoyl)-2,3-O-[(1-exo-allyloxy)-ethylidene]-D-glycero-beta-D-talo-oct-2-ulopyranos]onate, prepared from the 4-O-pNBz-protected Ko derivative, was elaborated into the alpha-Ko allyl ketoside, the reducing disaccharide alpha-Kdop-(2-->4)-Ko and the disaccharide alpha-Kdop-(2-->4)-Kop-(2-->OAll). Conversely, methyl[4,5,7,8-tetra-O-acetyl-3-O-(4-nitrobenzoyl)-alpha-D-glycero-D-talo-2-octulopyranosyl bromide]onate [Carbohydr. Res., 244 (1993) 69-84], was coupled with a Kdo acceptor to give the disaccharide alpha-Kop-(2-->4)-Kdop-(2-->OAll) after orthoester rearrangement and deprotection. The allyl glycosides were treated with cysteamine and converted into neoglycoproteins. The ligands correspond to inner core units from Acinetobacter haemolyticus and Burkholderia cepacia lipopolysaccharides.     

Synthesis of an octasaccharide fragment of high-mannose-type glycans of glycoproteins.

O-(alpha-D-Mannopyranosyl)-(1----2)-O-(alpha-D-mannopyranosyl)-(1----3)- O- [(alpha-D-mannopyranosyl)-(1----2)-O-(alpha-D-mannopyranosyl)-(1----6)]- O- (alpha-D-mannopyranosyl)-(1----6)-O-(beta-D-mannopyranosyl)-(1----4)-O-( 2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-2-deoxy- glucopyranose, an octasaccharide fragment of high-mannose type glycan of glycoproteins, was synthesized. Crucial glycosylation of trisaccharide intermediate, benzyl O-(2,4-di-O-benzyl-beta-D-mannopyranosyl)-(1----4)-O-(2-acetamido-3,6-di -O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-3,6-di-O-benz yl-2- deoxy-beta-D-glucopyranoside, was successful only with a di-O-acetyltetradeca-O-benzyl-D-mannopentaosyl chloride. The use of the corresponding hexadeca-O-acetyl-D-mannopentaosyl bromide did not give the desired product.     

Synthesis of O-alpha-L-fucopyranosyl-(1----3)-O-beta-D-galactopyranosyl-(1----4)-2- acetamido-2-deoxy-D-glucopyranose (N-acetyl-3'-O-alpha-L-fucopyranosyllactosamine)

Methyl 2-O-benzyl-beta-D-galactopyranoside (6) was obtained in five, good yielding steps from methyl beta-D-galactopyranoside (1). Treatment of 1 with tert-butylchlorodiphenylsilane in N,N-dimethylformamide in the presence of imidazole afforded a 6-(tert-butyldiphenylsilyl) ether, which was converted into its 3,4-O-isopropylidene derivative (3). Benzylation of 3 with benzyl bromide-silver oxide in N,N-dimethylformamide, and subsequent cleavage of its acetal and ether groups then afforded 6. On similar benzylation, followed by the same sequence of deprotection, benzyl 2-acetamido-3,6-di-O-benzyl-4-O-[6-O-(tert-butyldiphenylsilyl)-3,4 -O- isopropylidene-beta-D-galactopyranosyl]-2-deoxy-alpha-D-glucopyranoside gave the 2-O-benzyl derivative (10). Compound 10 was converted into its 4,6-O-benzylidene acetal (11). Glycosylation (catalyzed by halide-ion) of 11 with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide afforded the fully protected trisaccharide derivative (13). Cleavage of the benzylidene and then the benzyl groups of 13 furnished the title trisaccharide (16). The structure of 16 was established by 13C-n.m.r. spectroscopy.     

Synthesis and biological activities of octyl 2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-beta-L-fucopyranoside

Octyl 2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-beta-L-fucopyranoside, a fucosyl pentasaccharide with a regular structure resembling the repeating unit of a natural sulfated fucan, was chemically synthesized using a convergent '2+3' strategy. Regioselective 3-O-silylation of beta-thiofucopyranoside and AgOTf-catalyzed glycosylation of the protected glycosyl trichloroacetimidate facilitated a one-pot trisaccharide synthesis. The synthesized target compound showed good antitumor activity in vivo, and promising anticoagulant activity in vitro.     

p-Trifluoroacetamidophenyl O-alpha-D-mannopyranosyl-(1----3)-O-[alpha-D-mannopyranosyl- (1----6)]-beta-D-mannopyranoside

p-Nitrophenyl 2-O-benzyl-4,5-O-cyclohexylidene-beta-D-mannopyranoside (4) was condensed with tetra-O-benzoyl-alpha-D-mannopyranosyl bromide. The resulting, protected disaccharide was converted into p-nitrophenyl O-(2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl)-(1----3)-4-O-benzoyl-2-O- benzyl-beta-D-mannopyranoside (8), which was condensed with tetra-O-benzoyl-alpha-D-mannopyranosyl bromide to give p-nitrophenyl O-(2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl)-(1----3)-O -[2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl-(1----6)]-4-O-benzoyl-2-O -benzyl-beta-D-mannopyranoside (9) in 75% yield. Conversion of the p-nitrophenyl group followed by deprotection then yielded the title compound, whose structure was confirmed by 1H- and 13C-n.m.r. spectroscopy.     

Synthesis of a heptasaccharide fragment of the O-deacetylated GXM of C. neoformans serotype C

Beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->4)]-alpha-D-Manp, the fragment of the exopolysaccharide from Cryptococcus neoformans serovar C, was synthesized as its methyl glycoside. Thus, chloroacetylation of allyl 3-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranoside (1) followed by debenzylidenation and selective 6-O-benzoylation afforded allyl 2-O-chloroacetyl-3-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (4). Glycosylation of 4 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate (5) furnished the beta-(1-->4)-linked disaccharide 6. Dechloroacetylation gave the disaccharide acceptor 7 and subsequent coupling with 5 produced the trisaccharide 8. Deacetylation of 8 gave the trisaccharide acceptor 9 and subsequent coupling with a disaccharide 10 produced the pentasaccharide 11. Reiteration of deallylation and trichloroacetimidate formation from 11 yielded the pentasaccharide donor 12. Coupling of a disaccharide acceptor 13 with 12 afforded the heptasaccharide 14. Subsequent deprotection gave the heptaoside 16, while selective 2-O-deacetylation of 14 gave the heptasaccharide acceptor 15. Condensation of 15 with glucopyranosyluronate imidate 17 did not yield the expected octaoside, instead, an orthoester product 18 was obtained. Rearrangement of 18 did not give the target octaoside; but produced 15. Meanwhile, there was no reaction between 15 and the glycosyl bromide donor 19.     

Synthesis of (R)-2,3-epoxypropyl(1-->3)-beta-D-pentaglucoside

The title pentasaccharide was synthesized via a 2+3 strategy. The disaccharide donor, 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (8), was obtained by selective coupling of allyl 2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranoside with 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (4), followed by deallylation, and trichloroacetimidation. Meanwhile, the trisaccharide acceptor, allyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranoside (12), was prepared by coupling of allyl 2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranoside with 4, followed by deacetylation. Condensation of 8 with 12, followed by epoxidation, and deprotection, gave the target pentaoside.     

Synthesis of 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative structure of aescuflavoside A from the seeds of Aesculus chinensis

3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative flavonal glycoside named aescuflavoside A, isolated from the seeds of Aesculus chinensis, is synthesized via regioselective glycosylation of 7-O-benzyltamarixetin with glycosyl bromides under phase-transfer-catalyzed conditions.     

Synthesis of new sugar derivatives from Stachys sieboldi Miq and antibacterial evaluation against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus

A series of sugar derivatives (7-14) were synthesized from stachyose, a sugar compound of Stachys sieboldi Miq, and evaluated for antibacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus, and their structure-activity relationships were studied. The results showed that the compound OCT359 (allyl O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl)-(1-->6)-O-(2,3,4-tri-O-acetyl-alpha-D-galactopyranosyl)-(1-->6)-O-2,3,4-tri-O-acetyl-beta-D-glucopyranoside) (12) exhibited in vitro antibacterial activity. The allyl group at C-1 and the acetoxy groups of the manninotrioside were requisite for the antibacterial activity.     

Synthesis of alpha-series ganglioside GM1alpha containing C20-sphingosine

A synthesis of alpha-series ganglioside GM1alpha (III(6)Neu5AcGgOse4Cer) containing C20-sphingosine(d20:1) is described. Glycosylation of 2-(trimethylsilyl)ethyl 2,3,6-tri-O-benzyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside with the glucosamine donor ethyl 3-O-acetyl-2-deoxy-4,6-O-[(4-methoxyphenyl)methylene]-2-phthalimido-1-thio-beta-D-glucopyranoside furnished a beta-(1-->4)-linked trisaccharide. Reductive cleavage of the p-methoxybenzylidene group followed by intramolecular inversion of its triflate afforded the desired trisaccharide, which was transformed into a trisaccharide acceptor via removal of the phthaloyl and O-acetyl groups followed by N-acetylation. A tetrasaccharide acceptor was obtained by glycosylation of the trisaccharide acceptor with dodecyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-galactopyranoside, followed by removal of the p-methoxybenzyl group. Coupling of the tetrasaccharide acceptor with ethyl (methyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-1-thio-5-trichloroacetamido-D-glycero-D-galacto-2-nonulopyranosid)onate and subsequent radical reduction gave the desired GM1alpha saccharide derivative, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-eicosene-1,3-diol after conversion into the imidate.     

Synthesis of trisaccharides containing 3-deoxy-D-manno-2-octulosonic acid residues related to the KDO-region of enterobacterial lipopolysaccharides

Glycosylation of methyl (allyl 7,8-O-carbonyl-3-deoxy-alpha-D-manno-2-octulo-pyranosid)o nate with an alpha-(2----4) linked per-O-acetylated KDO-disaccharide bromide derivative under Helferich conditions afforded a 2:1 mixture of the alpha- and beta-linked trisaccharide derivatives in 50% yield. Removal of the protecting groups gave sodium O-[sodium (3-deoxy-alpha-D-manno-2-octulopyranosyl)onate]-(2----4)-O-[ sodium (3-deoxy-alpha- and -beta-D-manno-2-octulopyranosyl)onate]-(2----4)-sodium (allyl 3-deoxy-alpha-D-manno-2-octulopyranosid)onate. Radical copolymerization of the allyl glycosides afforded artificial antigens, suitable for defining antibody specificities directed against the KDO-region of enterobacterial lipopolysaccharides.     

Synthesis of spacer-containing chlamydial disaccharides as analogues of the alpha-Kdop-(2-->8)-alpha-Kdop-(2-->4)-alpha-Kdop trisaccharide epitope

On the basis of high-resolution crystal structures of the antigen binding fragment of the chlamydia-specific monoclonal antibody S25-2 in complex with the trisaccharide alpha-Kdop-(2-->8)-alpha-Kdop-(2-->4)-alpha-Kdop and part structures thereof, seven modified alpha-Kdop-(2-->8)-alpha-Kdop disaccharide derivatives were synthesized starting from the protected disaccharide allyl ketoside 1. Hydroboration and subsequent oxidation as well as ozonolysis, respectively, followed by Wittig-reaction for chain elongation were used to install a terminal carboxylic group on spacer entities of various chain lengths. Furthermore, addition of methyl 2-thioacetate to the allyl group furnished the corresponding thioether derivative. Standard deprotection gave the target disaccharides as simplified trisaccharide analogues, which will be used to probe the contribution of the proximal carboxylic group in the binding of chlamydia-specific di- and trisaccharide-reactive monoclonal antibodies.     

Regioselective glycosylation of 4,6-O-benzylidenated glucopyranosides

Regioselective glycosylation with allyl 4,6-O-benzylidene-alpha,beta-D-glucopyranoside or methyl 4,6-O-benzylidene-alpha,beta-D-glucopyranoside as the acceptor was investigated. It was found that the regioselectivity depends upon donor size and anomeric configuration of the acceptor, i.e., with a monosaccharide donor and an alpha-form acceptor, the (1-->3)-linked product was obtained predominantly or exclusively, while with disaccharide or trisaccharide donors and either an alpha or beta form acceptor, the (1-->2)-linked oligosaccharides were the only products.