Syntheses of methyl ethers of methyl α-D-mannopyranoside, and hydrogen bonding in diastereoisomers of methyl 4-O-(1-ethoxyethyl)-α-D-mannopyranoside

The synthesis of the 4-methyl, the 2,4-dimethyl, and the 2,3,6-trimethyl ethers of methyl α-D-mannopyranoside has been accomplished by the use of selective, benzoyl protecting groups, the 1-ethoxyethyl protecting group, and methylation with diazomethane. Considerable differences were noted in the i.r.- and n.m.r.-spectroscopic and t.l.c. properties of the diastereoisomers of methyl 4-O-[1-ethoxyethyl]-α-D-mannopyranoside. A structure, analogous to that of trans-decalin, maintained by intramolecular hydrogen-bonding is proposed for these compounds. The differences in physical properties of the two diastereoisomers are interpreted on the basis that the (R) isomer has an axially attached methyl group, and, therefore, the ring involved cannot be so stable as that of the (S) isomer.     

Studies on the koenigs-knorr reaction : Part V. Synthesis of 2-acetamido-2-deoxy-3-O-α-L-fucopyranosyl-α-D-glucose

Optically pure 2-acetamido-2-deoxy-3-O-α-L-fucopyranosyl-α-D-glucose was synthesized by the Koenigs-Knorr reaction of 2-O-benzyl-3,4-di-O-p-nitrobenzoyl-α-L-fucopyranosyl bromide with benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyrainoside. Reaction of 2,3,4-tri-O-acetyl-α-L-fucopyranosyl bromide gave the β-L-fucopyranosyl anomer. In contrast to the stereospecificity shown in this reaction by these two bromides, 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide afforded a mixture of α-L and β-L anomers in almost equimolar proportions. The disaccharides synthesized were crystallized and characterized, and their optical purity demonstrated by g.l.c. of the per(trimethylsilyl) ethers of the corresponding alditols.     

Synthesis of methyl 3-O- and 2-O-carbamoyl-α-D-mannopyranosides and carbamoyl-group migration between them

Methyl 3-O- and 2-O-carbamoyl-α-D-mannopyranosides, (2 and 3), were synthesized from methyl α-D-mannopyranoside via ammonolysis of a cyclic carbonate or a p-nitrophenoxycarbonate, as shown in Charts 1 and 2. Carbamoyl-group migration between the C-2 and C-3 hydroxyl groups, in methyl α-D-mannopyranoside under alkaline conditions, was also studied.     

Unsaturated sugars I. Decarboxylative elimination of methyl 2,3-di-O-benzyl-α-D-glucopyranosiduronic acid to methyl 2,3-di-O-benzyl-4-deoxy-β-L-threo-Pent-4-enopyranoside

Decarboxylative elimination of methyl 2,3-di-O-benzyl-α-D-glucopyranosiduronic acid (1) with N,N-dimethylformamide dineopentyl acetal in N,N-dimethylformamide gave methyl 2,3-di-O-benzyl-4-deoxy-β-L-threo-pent-4-enopyranoside (3). Debenzylation of 3 was effected with sodium in liquid ammonia to give methyl 4-deoxy-β-L-threo-pent-4-enopyranoside (4). Hydrogenation of 3 catalyzed by palladium-on-barium sulfate afforded methyl 2,3-di-O-benzyl-4-deoxy-β-L-threo-pentopyranoside (5), whereas hydrogenation of 3 over palladium-on-carbon gave methyl 4-deoxy-β-L-threo-pentopyranoside (6). An improved preparation of methyl 4,6-O-benzylidene-α-D-glucopyranoside is also described.     

Synthesis of and glycosidase inhibition by α-l-homofuconojirimycin

The first synthesis of the novel azasugar α-l-homofuconojirimycin is reported. The biological activity of this compound is described and is shown to be more specific for α-l-fucosidase than compounds previously tested.     

Preferential sulfonylation of methyl 2,6-di-O-mesyl-α-D-glucopyranoside

When equimolar ratios of mesyl chloride and methyl 2,6-di-O-mesyl-α-D-glucopyranoside were allowed to react in pyridine and the product resolved by preparative t.l.c., the 2,6-di-, 2,3,6-tri-, 2,4,6-tri-, and 2,3,4,6-tetra-mesyl esters were obtained in (0.5–0.6):1:(4–5):(1-2-1.4) molar ratio. Benzoylation of either the isolated 2,4,6-tri-O-mesyl ester or, more conveniently, the mixture from monomesylation gave the crystalline methyl 3-O-benzoyl-2,4,6-triO-mesyl-α-D-glucopyranoside (8). As both of these trimesyl esters (7 and 8) are unreported, isolation of the benzoate established the 2,4,6-ester arrangement, and the 2,3,6-triester was prepared by standard methods. Treating methyl α-D-glucopyranoside with 3 molar equivalents of mesyl chloride and, subsequently, with 1 molar equivalent of benzoyl chloride, proved a convenient method for preparing the 3-O-benzoyl derivative in moderate yield. Monotosylation of methyl 2,6-di-O mesyl-α-D-glucopyranoside was not so definitive as mesylation, but a molar ratio of 1:2.8 for the 3-O-tosyl:4-O-tosyl product was derived from n.m.r. data. This work, when combined with literature reports, establishes that, in methyl α-D-glucopyranoside, the reactivity toward sulfonylation is 6-OH>2-OH>4-OH>3-OH.     

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.     

Product-identification and substrate-specificity studies of the GDP-l-fucose: 2-acetamido-2-deoxy-β-d-glucoside (fuc→asn-linked GlcNAc) 6-α-l-fucosyltransferase in a golgi-rich fraction from porcine liver

Golgi-rich membranes from porcine liver have been shown to contain an enzyme that transfers l-fucose in α-(1→6) linkage from GDP-l-fucose to the asparagine-linked 2-acetamido-2-deoxy-d-glucose r residue of a glycopeptide derived from human α₁-acid glycoprotein. Product identification was performed by high-resolution, ¹H-n.m.r. spectroscopy at 360 MHz and by permethylation analysis. The enzyme has been named GDP-l-fucose: 2-acetamido-2-deoxy-β-d-glucoside (Fuc→Asn-linked GlcNAc) 6-α-l-fucosyltransferase, because the substrate requires a terminal β-(1→2)-linked GlcNAc residue on the α-Man (1→3) arm of the core. Glycopeptides with this residue were shown to be acceptors whether they contained 3 or 5 Man residues. Substrate-specificity studies have shown that diantennary glycopeptides with two terminal β-(1→2)-linked GlcNAc residues and glycopeptides with more than two terminal GlcNAc residues are also excellent acceptors for the fucosyltransferase. An examination of four pairs of glycopeptides differing only by the absence or presence of a bisecting GlcNAc residue in β-(1→4) linkage to the β-linked Man residue of the core showed that the bisecting GlcNAc prevented 6-α-l-fucosyltransferase action. These findings probably explain why the oligosaccharides with a high content of mannose and the hybrid oligosaccharides with a bisecting GlcNAc residue that have been isolated to date do not contain a core l-fucosyl residue.     

Efficient synthesis of d-xylo and d-ribo-phytosphingosines from methyl 2-amino-2-deoxy-β-d-hexopyranosides

A general and flexible synthetic approach to biologically important 5,6-unsaturated C₁₈-phytosphingosines was developed via olefin cross-metathesis employing truncated C₆-phytosphingosines as the key intermediates. These were efficiently prepared in high yields by zinc-mediated reductive opening of methyl 2-amino-2-deoxy-β-hexopyranosides.

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Application of the imidate procedure to α-d-galactosyltion

Using the imidate procedure, 2,3,4,6-tetra-O-benzyl-1-O-(N-methylacetimidoyl)-β-d-galactopyranose was condensed with various monosaccharides to provide, in good yield and with high stereoselectivity, α-linked disaccharides.     

A method for the determination of the pKa of α-n-benzoyl-l-arginine in the presence of an impurity

A method is proposed for the simultaneous detection and determination of minor impurities in weak acid (or bases) along with the evaluation of all relevant pK′s. By use of the method described, the pK′s of α-n-benzoyl-l-arginine and α,ω-dibenzoyl-l-arginine have been accurately determined in the same solution. These values are 3.31 for α-n-benzoyl-l-arginine and 2.24 for α,ω-dibenzoyl-l-arginine. This latter compound was found to exist as a 5.3% impurity in a commercial preparation of α-n-benzoyl-l-arginine.