Derivatives of β-D-fructofuranosyl α-D-galactopyranoside

De-etherification of 6,6′-di-O-tritylsucrose hexa-acetate (2) with boiling, aqueous acetic acid caused 4→6 acetyl migration and gave a syrupy hexa-acetate 14, characterised as the 4,6′-dimethanesulphonate 15. Reaction of 2,3,3′4′,6-penta-O-acetylsucrose (5) with trityl chloride in pyridine gave a mixture containing the 1′,6′-diether 6 the 6′-ether 9, confirming the lower reactivity of HO-1′ to tritylation. Subsequent mesylation, detritylation, acetylation afforded the corresponding 4-methanesulphonate 8 1′,4-dimethanesulphonate 11. Reaction of these sulphonates with benzoate, azide, bromide, and chloride anions afforded derivatives of β-D-fructofuranosyl α-D-galactopyranoside (29) by inversion of configuration at C-4. Treatment of the 4,6′-diol 14 the 1,′4,6′-triol 5, the 4-hydroxy 1′,6′-diether 6 with sulphuryl chloride effected replacement of the free hydroxyl groups and gave the corresponding, crystalline chlorodeoxy derivatives. The same 4-chloro-4-deoxy derivative was isolated when the 4-hydroxy-1′,6′-diether 6 was treated with mesyl chloride in N,N-dimethylformamide.     

α-D-Mannosidase-catalyzed hydrolysis of substituted phenyl α-D-mannopyranosides

The influence substituents on the hydrolysis of substituted phenyl α-D-mannopyranosides by α-D-mannosidase from Medicago sativa L. has been investigated. As indicated by structure-activity relations, the electronic effect of the substituent has an influence on the rate of formation of the intermediate mannosyl-enzyme complex. This effect depends not only on the nature of the substituent, but also on its position (meta or para) and on the temperature of the experiment. Hammett-type linear free energy relationships show that the reaction constant p changes its sign at ～27°. Substrates with strong electron-withdrawing groups show values of log V that are linearly related to 1/T, whereas the Arrhenius plots for other substrates are severely curved. This complex behaviour is tentatively explained by assuming that some meta-substituents have an unusual, temperature- and substituent-dependent influence on the formation of the Michaelis—Menten complex.     

Monomolar acetalations of methyl α-d-mannosides—synthesis of methyl α-d-talopyranoside

Methyl α-d-mannopyranoside (1 mole) reacts with 2,2-dimethoxypropane (1 mole), to give the 4,6-O-isopropylidene derivative (2) which rearranges to the 2,3-O-isopropylidene derivative (4). Compound4 can also be prepared by graded hydrolysis of methyl 2,3:4,6-di-O-isopropylidene-α-d-mannopyranoside. Successive benzoylation, oxidation, and reduction of4 provides a useful route to a number ofd-talopyranoside compounds. Methyl α-d-mannofuranoside (1 mole) reacts with 1–2 moles of 2,2-dimethoxypropane to give the 5,6-O-isopropylidene derivative (16) in 90% yield.     

Identification of neoschaftoside as 6-C-β-d-glucopyranosyl-8-C-β-l-arabinopyranosylapigenin

The structure of neoschaftoside is shown for the first time to be 6-C-β-d-glucopyranosyl-8-C-β-l-arabinopyranosylapigenin. A variety of chemical and spectroscopic techniques are involved.     

Synthesis of 4-O-α-d-galactopyranosyl-l-rhamnose and 4-O-α-d-galactopyranosyl-2-O-β-glucopyranosyl-l-rhamnose using dioxolane-type benzylidene acetals as temporary protecting-groups

The Halide ion-catalysed reaction of benzyl exo-2,3-O-benzylidene-α-l-rhamnopyranoside with tetra-O-benzyl-α-d-galactopyranosyl bromide and hydrogenolysis of the exo-benzylidene group of the product 2 gave benzyl 3-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl)-α-l-rhamnopyranoside (6). Compound 2 was converted into 4-O-α-d-galactopyranosyl-l-rhamnose. The reaction of 6 with tetra-O-acetyl-α-d-glucopyranosyl bromide and removal of the protecting groups from the product gave 4-O-α-d-galactopyranosyl-2-O-β-d-glucopyranosyl-l-rhamnose.     

Synthesis of 4-O-β-D-mannopyranosyl-L-rhamnopyranose

The title disaccharide (16) has been synthesized in 50% overall yield by way of condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-α-D-mannopyranosyl bromide 5 with methyl 2,3-O-isopropylidene-α-L-rhamnopyranoside (1) in chloroform solution, in the presence of silver oxide. The disaccharide was characterized as the crystalline isopropyl alcoholate of methyl 4-O-β-D-mannopyranosyl-α-L-rhamnopyranoside (11) and as 1,2,3-tri-O acetyl-4-O- (2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-α-L-rhamnopyranose (15). Methyl β-D-mannopyranoside isopropyl alcoholate 7 was readily obtained in 85% yield via the reaction of bromide 5 with methanol.Reduction of 2,3-di-O-methyl-L-rhamnose with sodium borohydride, followed by acetylation, may result in the formation of an appreciable proportion of a boric ester, namely 1,5-di-O-acetyl-4-deoxy-2,3-di-O-methyl-L-rhamnitol-4-yl dimethyl borate, depending on the procedure used.     

Synthesis of 5-O-β-D-galactofuranosyl-D-galactofuranose

Conversion of benzyl αβ-D-galactofuranoside into the 5,6-O-[α-(dimethyl-amino)benzylidene] derivative, followed by acetylation of HO-2 and HO-3, and selective ring opening or the acetal, gave benzyl 2,3-di-O-acetyl-6-O-benzoyl-αβ-D-galactofuranoside(4). The title disaccharide was synthesised from4 by reaction with 3,4,6-tri-O-acetyl-α-D-galactofuranose 1,2-(methyl orthoacetate) followed by removal of protecting groups     

β-d-glucosidase-catalysed transfer of the glycosyl group from aryl β-d-gluco- and β-d-xylo-pyranosides to phenols

The effect of phenols on the hydrolysis of substituted phenyl β-d-gluco- and β-d-xylo-pyranosides by β-d-glucosidase from Stachybotrys atra has been investigated. Depending on the glycon part of the substrate and on the phenol substituent, the hydrolysis is either inhibited or activated. With aryl β-d-xylopyranosides, transfer of the xylosyl residue to the phenol, with the formation of new phenyl β-d-xylopyranosides, is observed. With aryl β-d-glucopyranosides, such transfer does not occur when phenols are used as acceptors, but it does occur with anilines. A two-step mechanism, in which the first step is partially reversible, is proposed to explain these observations. A qualitative analysis of the various factors determining the overall effect of the phenol is given.     

Stereoselective hydrogenolysis of dioxolane-type benzylidene derivatives: Synthesis of some benzyl ethers of benzyl β-d-arabinopyranoside

The following derivatives of benzyl β-d-arabinopyranoside are described: exo-3,4-O-benzylidene (2), endo-3,4-O-benzylidene (3), and the 2-benzyl ether derivatives (4 and 5) of 2 and 3. Hydrogenolysis (LiAlH₄-AlCl₃) of the exo-isomers (2 and 4) gave mainly 4-hydroxy-3-O-benzyl derivatives (6 and 11), whereas the endo-isomers (3 and 5) gave mainly 3-hydroxy-4-O-benzyl derivatives (7 and 12). Acid hydrolysis of 4 and 5 yielded the 2-O-benzyl derivative (10).     

Chemical Syntheses of 4-O-α and -β-D-galactopyranosyl-D-galactose and 3-O-α- and -β-D-galactopyranosyl-D-galactose

Reaction of 2,3-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (2) with 2,3,4,6-tetra- O-acetyl-α-D-galactopyranosyl bromide in the presence of mercuric cyanide and subsequent acetolysis gave 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (4, 40%) and 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (5, 30%). Similarly, reaction of 2,4-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (3) gave 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (6, 46%) and 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (7, 14%). The anomeric configurations of 4-7 were assigned by n.m.r. spectroscopy. Deacetylation of 4-7 afforded 4-O-α-D-galactopyranosyl-D-galactose (8), 4-O-β-D-galactopyranosyl-D-galactose (9), 3-O-α-D-galactopyranosyl-D-galactose (10), and 3-O-β-D-galactopyranosyl-D-galactose (11), respectively.     

The use of 1-O-tosyl-d-glucopyranose derivatives in α-d-glucoside synthesis

1-O-Tosyl-d-glucopyranose derivatives having a nonparticipating benzyl group at O-2 have been shown to react rapidly in various solvents with low concentrations of alcohols, either methanol or methyl 2,3,4-tri-O-benzyl-α-d-glucopyranoside. The stereospecificity of the glucoside-forming reaction could be varied from 80% of β to 100% of α anomer by changing the solvent or modifying the substituents on the 1-O-tosyl-d-glucopyranose derivative. 2,3,4-Tri-O-benzyl-6-O-(N-phenylcarbamoyl)-1-O-tosyl-α-d-glucopyranose in diethyl ether gave a high yield of α-d-glucoside. Kinetic measurements of reaction with various alcohols (methanol, 2-propanol, and cyclohexanol) show a high rate even at low concentrations of alcohol, and give some insight into the reaction mechanism. The high rate and stereoselectivity of their reaction suggest that the 1-O-tosyl-d-glucopyranose derivatives may be used as reagents for oligosaccharide synthesis.     

Nucleophilic displacements of methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-α-d-lyxo- and -β-l-ribo-pyranosides,and deamination of the corresponding 4-amino sugars

Reinvestigation of the reaction of methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-α-d-lyxopyranoside (4) with azide ion has shown that methyl 4-deoxy-2,3-O-isopropylidene-β-l-erythro-pent-4-enopyranoside (8, ～51.5%) is formed, as well as the azido sugar 7 (～48.5%) of an S_N2 displacement. The unsaturated sugar 8 was more conveniently prepared by heating the sulphonate 4 with 1,5-diazabicyclo-[5.4.0]undec-5-ene. An azide displacement on methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-β-l-ribopyranoside (12) furnished methyl 4-azido-4-deoxy-2,3-O-isopropylidene-α-d-lyxopyranoside (13, ～66%) and the unsaturated sugar 14 (～28.5%), which was also prepared by heating the sulphonate with 1,5-diazabicyclo[5.4.0]undec-5-ene. Deamination of methyl 4-amino-4-deoxy-2,3-O-isopropylidene-α-d-lyxopyranoside (5), prepared by reduction of 13, with sodium nitrite in 90% acetic acid at ～0°, yielded methyl 2,3-O-isopropylidene-α-d-lyxopyranoside (10a, 26.2%), methyl 2,3-O-isopropylidene-β-l-ribofuranoside (21a, 18.4%), and the corresponding acetates 10b (34.5%) and 21b (21.3%). These products are considered to arise by solvolysis of the bicyclic oxonium ion 29, formed as a consequence of participation by the ring-oxygen atom in the deamination reaction. Similar deamination of methyl 4-amino-4-deoxy-2,3-O-isopropylidene-β-l-ribopyranoside (6) afforded, exclusively, the products 10a (34.4%) and 10b (65.6%) of inverted configuration. Deamination of methyl 5-amino-5-deoxy-2,3-O-isopropylidene-β-d-ribofuranoside (20) gave 22ab, but no other products. An alternative synthesis of the amino sugars 5 and 6 is available by conversion of 10a into methyl 2,3-O-isopropylidene-β-l-erythro-pentopyranosid-4-ulose (11), followed by reduction of the derived oxime 15 with lithium aluminium hydride.     

Crystal structures of rare disaccharides, α-d-glucopyranosyl β-d-psicofuranoside, and α-d-galactopyranosyl β-d-psicofuranoside

The crystal structures of α-d-glucopyranosyl β-d-psicofuranoside and α-d-galactopyranosyl β-d-psicofuranoside were determined by a single-crystal X-ray diffraction analysis, refined to R₁ = 0.0307 and 0.0438, respectively. Both disaccharides have a similar molecular structure, in which psicofuranose rings adopt an intermediate form between ⁴E and ⁴T₃. Unique molecular packing of the disaccharides was found in crystals, with the molecules forming a layered structure stacked along the y-axis.     

The use of positively charged leaving-groups in the synthesis of α-D-linked glucosides. Synthesis of methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside

Quaternary ammonium and triphenylphosphonium salts of 2,3,4-tri-O-benzyl-6-O-(N-phenylcarbamoyl)-D-glucopyranosyl bromide were readily prepared by reaction with tertiary amines and triphenylphosphine under anhydrous conditions. Methanolysis of these salts was studied to determine the conditions of solvent and temperature that would produce the highest yields of α-D-glucosides. The quaternary ammonium salts gave the highest yields with solvents of low dielectric constant and room temperature. The phosphonium salts gave moderate yields with diethyl ether at 50°. The synthesis of methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside by treatment of the quaternary ammonium salt of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide with methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside was studied as a model for the synthesis of oligosaccharides. The anomeric composition of the disaccharide product could be easily determined from the optical rotation since the specific rotations of both the final product and of the gentiobioside analog are known. Under the best conditions, the yield of disaccharide was low (50%) and the reactions were not completely stereoselective.     

A synthesis of 3-O-(α-d-mannopyranosyl)-d-mannose and its protein conjugate

Methods for the synthesis of 3-O-(α-d-mannopyranosyl)-d-mannose and 2-(4-aminophenyl)ethyl 3-O-(α-d-mannopyranosyl)-α-d-mannopyranoside have been investigated by a number of sequences. Glycosidations with 2,3-di-O-acetyl-4,6-di-O-benzyl-d-mannopyranosyl and 2-O-benzoyl-3,4,6-tri-O-benzyl-d-mannopyranosyl p-toluenesulfonates were found to give better yields than the Helferich modification, the use of a peracylated d-mannopyranosyl halide, or the use of triflyl leaving group. Only the α anomer was obtained. Factors influencing glycosidation reactions are discussed. A mercury(II) complex was used for selective 2-O-acylation of 4,6-di-O-benzyl-α-d-mannopyranosides. A disaccharide—protein conjugate was prepared by the isothiocyanate method.     

The oxidation of methyl α-D-glucopyranoside with methyl sulproxide and acetic anhydride

The relative proportions of carbonyl, O-acetyl, and O-(methylthio)methylsugars resulting from the partial oxidation of methyl α-D-glucopyranoside with methyl sulphoxide and acetic anhydride have been investigated@ the preparation of the 2- and 6-(methylthio)methyl ethers of methyl α-D-glucopyranoside is described.     

Synthesis of p-isothiocyanatophenyl 3-O-(3,5-dideoxy-α-d-ribo-hexopyranosyl)-α-d-mannopyranoside

The synthesis of the title disaccharide derivative (1C), corresponding to the Salmonella O-factor 2¹, is described. Treatment of 2-O-benzyl-4-O-p-nitrobenzoyl-α-paratosyl bromide (5) with p-nitrophenyl 2-O-benzyl-4,6-O-benzylidene-α-d-mannoside in dichloromethane, in the presence of mercuric cyanide, gave the α- and β-linked disaccharide derivatives (6a and 6b) in yields of 34 and 5%, respectively. The disaccharide derivative 10 can react with free amino groups in proteins to produce artificial antigens useful in studies on Salmonella immunology.     

The acid-catalyzed hydrolysis of β-d-xylofuranosides

The rate constants for the hydrolysis of six alkyl and four aryl β-d-xylofuranosides in aqueous perchloric acid at various temperatures have been measured. The effects of varying the aglycon structure on the hydrolysis rate are interpreted in terms of two concurrent reactions. Either, the substrate, protonated on the glycosidic oxygen atom, undergoes a rate-limiting heterolysis to form a cyclic oxocarbonium ion, or, an initial rapid protonation of the ring oxygen is followed by a unimolecular cleavage of the five-membered ring, all subsequent reactions being fast. It is suggested that xylofuranosides having strongly electron-attracting aglycon groups react mainly by the former pathway, whereas the latter is more favourable for substrates having electron-repelling aglycon groups. The negative entropies of activation obtained with the latter compounds are attributed to the rate-limiting opening of the five-membered ring. The rate variations of the hydrolyses of alkyl β-d-xylofuranosides in aqueous perchloric acid-methyl sulfoxide mixtures are interpreted as lending further support for the suggested chance in mechanism.     

Short synthetic sequence for 2-sulfation of α-l-iduronate glycosides

Hunter syndrome (mucopolysaccharidosis-II) is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. The assay of this sulfatase requires the use of α-l-iduronate glycosides containing a sulfate at the 2-position. We report a simple, three-step procedure for the introduction of sulfate at the 2-position starting with the methyl ester of α-l-iduronate glycosides. The procedure involves protection of the 2- and 4-hydroxyl groups of the iduronate moiety as the dibutyl stannylene acetal, selective sulfation with sulfur trioxide-trimethylamine, and deprotection of the methyl ester to afford the desired 2-sulfate in 61% overall yield.