Zoltán Szurmai

Synthesis of p-trifluoroacetamidophenyl 6-deoxy-2-O-3-O- [2-O-methyl-3-O-(2-O-methyl-α-d-rhamnopyranosyl)- α-l-fucopyranosyl]-α-l-rhamnopyranosyl-α-l- talopyranoside: a spacer armed tetrasaccharide glycopeptidolipid antigen of Mycobacterium avium serovar 20

Abstract The synthesis of the title tetrasaccharide glycoside 38 is reported. p -Nitrophenyl endo -3,4- O -benzylidene-6-deoxy-α- l -talopyranoside ( 4 , 3- O -acetyl-2,4-di- O -benzyl-α- l -rhamnopyranosyl trichloroacetimidate ( 7 ), methyl 3- O -acetyl-4- O -benzyl-2- O -methyl-1-thio-β- l -fucopyranoside ( 15 ) 3- O -acetyl-4- O -benzyl-2- O -methyl-α- l -fucopyranosyl bromide ( 16 ), and ethyl 3- O -acetyl-4- O -benzyl-2- O -methyl-1-thio-α- d -rhamnopyranoside ( 33 ) were prepared as intermediates. Compound 4 was glycosylated with imidate 7 as well as with methyl 3- O -acetyl-2,4-di- O -benzyl-1-thio-α- l -rhamnopyranoside ( 9 ), affording the same disaccharide derivative 8 . Deacetylation of 8 gave crystalline 17 . Condensation of 17 with both fucosyl donors 15 and 16 yielded the same trisaccharide derivative 18 stereoselectively. Compound 18 was also prepared by the coupling of 4 with disaccharide glycosyl donor 20 . After deacetylation of 18 (→ 34 ), methyl triflate-promoted glycosylation with compound 33 resulted in tetrasaccharide 35 . Conversion of the p -nitrophenyl group of 35 into the p -trifluoroacetamidophenyl group (→ 36 ) and removal of the protecting groups gave the title tetrasaccharide glycoside 38 .

4,6-di-O-benzoyl-3-O-benzyl-α-d-arabino-hexopyranos-2-ulosyl bromide: A conveniently accessible glycosyl donor for the expedient construction of diantennary β-d-mannosides branched at O-3 and O-6

A concise practical, large scale-adaptable six-step sequence has been developed for the transformation of diacetone-glucose into 4,6-di-O-benzoyl-3-O-benzyl-alpha-D-arabino-hexopyranos-2-ulosy l bromide (7), a most useful indirect beta-D-mannosyl donor as its blocking group pattern allows the construction of biologically relevant beta-D-mannosides branched at O-3 and O-6. The broad utility of this new ulosyl bromide 7 resides in its high anomeric reactivity, and in the ease and uniformity with which beta-stereocontrol can be achieved over both, glycosidations and carbonyl reduction of the beta-ulosides formed: Koenigs-Knorr conditions exclusively provide beta-glycosiduloses, hydride reduction of their carbonyl functions proceeds with high stereoselectivities (> 20:1) in favor of the beta-D-mannosides. These preparatively auspicious properties are materialized in an efficient, straightforward synthesis of alpha-D-Manp-(1-->6)-[alpha-D-Manp-(1-->3)]-beta-D-Manp++ +-(1-->O)-Octyl, the 3,6-O-branched core-mannotrioside carrying an octyl spacer instead of the chitobiosyl unit.

Synthesis of 2-O-α-, 3-O-α-, 3-O-β-, and 4-O-α-l-rhamnopyranosyl-d-galactose

Condensation of benzyl 3-O-benzoyl-4,6-O-benzylidene-, benzyl 2-O-benzoyl-4,6-O-benzylidene- (2), and benzyl2,3,6-tri-O-benzyl-⨿-d-galactopyranoside, separately, with tri-O-acetyl-α-l-rhamnopyranosyl bromide gave mainly α-linked disaccharide derivatives. An appreciable proportion of the ⨿-linked disaccharide was also obtained from 2. An anomalous deacylation reaction was found for the (1→3)-linked disaccharide, and the partially benzoylated products were isolated and characterised. The anomeric configuration of each disaccharide was established on the basis of JC-1,H-1 values. The chemical shifts for the galactose moieties of the α- and β-l-rhamnopyranosyl derivatives differed in a systematic way.

Anomalous Zemplén deacylation reactions of 2-O-acyl-3-O-alkyl or -3-O-glycosyl derivatives of d-galactose and d-glucose: synthesis of O-α-d-mannopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→3)-d-galactose and an intermediate for the preparation of 2-O-glycosyl-3-O-(α-d-mannopyranosyl)-d-glucoses

Abstract Treatment of 2- O -benzoyl ( 1 ) and 2- O -acetyl ( 5 ) derivatives of benzyl 4,6- O -benzylidene-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-β- d -galactopyranoside under Zemplen conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated disaccharides in which the 2- O -acyl groups were retained. Likewise, a similar result was obtained with the β- l -rhamnopyranosyl analogue ( 3 ) of 1 . This anomalous reaction was used in a synthesis of the title trisaccharide ( 17 ) and of methyl 4,6- O -benzylidene-3- O -(2,3:4,6-di- O -isopropylidene-α- d -mannopyranosyl)-α- d -glucopyranoside, an intermediate for the synthesis of 2- O -glycosyl-3- O -(α- d -mannopyranosyl)- d -glucoses.

Anomalous Zemplén deacylation reactions of α- and β-d-mannopyranoside derivatives

Abstract Reaction of mono-, di-, and trisaccharide derivatives of methyl β- d - and octyl β- d -mannopyranosides bearing ester groups at isolated and non-isolated positions on the same molecule, under Zemplen conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated compounds, in which the O -acyl groups were retained at isolated sites. In the case of one disaccharide, all the benzoyl groups remained intact at the reducing end, while all the acetyl functions were removable from the nonreducing end. In another case, both isolated ester groups at positions 2 and 4 were retained at the reducing end. The isolated 2- O -acyl groups on methyl α- d -mannopyranoside compounds were more labile than on the corresponding β-mannosides under the same conditions. The mechanism of the reaction may be different for ester groups at isolated or non-isolated positions. In the latter case, acyl migration may take place and carry acyl groups into a less hindered position.

13C-NMR study of methyl- and benzyl ethers of l-arabinose and oligasaccharides having l-arabinose at the reducing end. Synthesis of 2-O-β-d-glucopyranosyl-, 2-O-α-l-rhamnopyranosyl-, 3-O-β-d-glucopyranosyl-2- O-α-l-rhamnopyranosyl- and 4-O-β-d-glucopyranosyl-2-O-α-l-rhamnopyranosyl-l-arabinose

Abstract The reaction of benzyl exo -3,4-O-benzylidene-β- l -arabinopyranoside 1 with α-acetobromo- d -glucose 3 resulted in a mixture of two disaccharides, 5 and 6 , in which the configuration of the acetal ring was different. The reaction of 1 with α-acetobromo- l -rhamnose 4 gave the desired disaccharide 7 without isomerisation of the dioxolane-type benzylidene ring. The reason for the isomerisation, occuring during the Koenigs-Knorr reaction, is discussed. Similar treatment of benzyl endo -3,4-O-benzylidene-β- l -arabinopyranoside 2 with 4 yielded 8 . Compounds 6 , 7 and 8 were deacetylated and benzylated to obtain 9 , 10 and 11 . Hydrogenolysis (LiAlH 4 AlCl 3 ) of all fully protected disaccharides afforded derivatives with a free OH-3 ( 9 → 13 and 11 → 15 ). Hydrogenolysis of 10 also resulted in 15 , and the desired 14 with a free OH-4 was only the minor product of the reaction. Glucosylation of compounds 14 and 15 resulted in the two trisaccharide derivatives in protected form ( 16 and 17 ). Deprotection of 6 , 7 , 16 and 17 gave the four title compounds ( 22 , 23 , 18 and 19 ). The synthesized compounds were studied by 1 H- and 13 C-NMR spectroscopic methods. In disaccharides having (1 → 2) bonds and in trisaccharide 19 having (1 → 2) and (1 → 3) bonds the arabinose moiety is present in pyranose and furanose forms. The complex spectra of these derivatives were assigned using the methyl ethers of l -arabinose ( 24–29 ) as model compounds. The 13 C-NMR spectrum of 18 was assigned with the aid of 4-O-β- d -glucopyranosyl- l -arabinopyranose. For comparisons, the spectra of all mono- and dibenzyl ethers of benzyl β- l -arabinopyranoside were also recorded and assigned.

Synthesis and 13C-N.M.R. spectroscopy of 2-O- and 6-O-acetyl-3-O-α-l-rhamnopyranosyl-d-galactose, constituents of bacterial cell-wall polysaccharides

Abstract Benzyl 2- O -acetyl-4,6- O -benzylidene-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-β- d -galactopyranoside ( 11 ) has been synthesised by two routes. Partial deacetylation of 11 and then acid hydrolysis yielded benzyl 2- O -acetyl-3- O -α- l -rhamnopyranosyl-β- d -galactopyranoside, catalytic hydrogenolysis of which gave the first title compound in excellent yield. Benzyl 4,6- O -benzylidene-3- O -α- l -rhamnopyranosyl-β- d -galactopyranoside was benzylated, and hydrogenolysis (LiAlH 4 -AlCl 3 ) of the product gave the disaccharide derivative 16 with only HO-6 unsubstituted. Acetylation of 16 followed by catalytic hydrogenolysis gave the crystalline, second title compound. As model compounds for comparative n.m.r. studies, 2- O -, 3- O -, and 6- O -acetyl- d -galactose were also synthesised.

Synthesis and hydrogenolysis of the methylene, ethylidene, isopropylidene, and diastereoisomeric 1-phenylethylidene acetals of β-l-arabino- and α-l-rhamnopyranoside derivatives

Abstract Both diastereoisomers of 1-phenylethylidene acetals (acetophenone acetals) of methyl and benzyl β- l -arabinopyranoside and α- l -rhamnopyranoside were prepared. Acetal-exchange reactions gave only the endo -phenyl isomers; their 2- O - and 4- O -acetyl derivatives were isomerised into the exo -phenyl compounds. 1 H-N.m.r. data were used to determine the absolute configuration at the acetal carbon atom in these compounds. The protons of the methyl group of the exo -phenyl isomers resonate at lower field than those of the endo -phenyl isomers. Hydrogenolysis of various methylene, ethylidene, and isopropylidene derivatives gave axial ethers. The endo -phenyl isomers of the acetophenone derivatives also gave axial 1-phenylethyl ethers in two diastereoisomeric forms. The exo -phenyl isomers of the arabinosides were stable towards the reagent (LiAlH 4 AlCl 3 ), whereas the corresponding rhamnopyranosides gave the 2-(1-phenylethyl) ethers, but cleavage required prolonged reaction time and higher temperature.

New Factors Governing Stereoselectivity in Borohydride Reductions ofβ‐D‐Glycoside‐2‐uloses − The Peculiar Effect of “Activated” DMSO

Comparative evaluation of the manno/gluco ratios obtained in the conventional reductions of β-D-glucoside-2-uloses (1−4, 13 and 14) reveals the influence of the substitution pattern: the presence of a 4,6-O-acetal function results in lower stereoselectivity in the monosaccharide-uloside cases and low stereoselectivity in the disaccharide-uloside cases, while the absence of a 4,6-O-acetal group provides distinctly higher stereoselectivity. The 3-O-benzyl and 3-O-allyl ethers vicinal to the carbonyl to be reduced have a similar influence on the steric outcome of the carbonyl reduction. A peculiar effect of acetoxydimethylsulfonium acetate (“activated” DMSO) was observed. In all cases, its presence strongly increased the manno-selectivity of the reduction. A simple, preparatively expedient, commonly suitable protocol has been elaborated for achieving high manno-selectivities and, hence, satisfactory yields.

Glycan microarrays : new angles and new strategies

Carbohydrate microarrays, comprising hundreds to thousands of different glycan structures on solid surfaces in a spatially discrete pattern, are sensitive and versatile tools for the analysis of glycosylation changes in complex biological samples. Glycoarrays are also suitable for monitoring multiple molecular interactions with biomolecules where sugars are involved, offering a large variety of bioassay options. In this paper we review the most important glycan microarray types currently used with their main applications, and discuss some of the future challenges the technology faces.