Selenium derivatives of L-arabinose, D-ribose,and D-xylose

Attempted cyclization of 2,3,4-tri-O-methyl-5-seleno-L-arabinose dimethyl acetal in acidic solution gave the corresponding diselenide. Intramolecular attack by the selenobenzyl group at C-5 of 5-O-p-tolylsulfonyl-L-arabinose dibenzyl diseleno-acetal resulted in the formation of benzyl 1,5-diseleno-L-arabinopyranoside. Similarly, 2,3,5-tri-O-methyl-4-O-p-tolylsulfonyl-D-xylose dibenzyl diselenoacetal gave benzyl 2,3,5-tri-O-methyl-1,4-diseleno-L-arabinofuranoside, and 2,3,4-tri-O-acetyl-5-O-p-tolylsulfonyl-D-xylose (or ribose) dibenzyl diselenoacetal gave benzyl 2,3,4-tri-O-acetyl-1,5-diseleno-D-xylo- (or ribo-)pyranoside. The glycosylic benzylseleno group was removed from the pyranoside with mercuric acetate, but attempted deacetylation of the product led to decomposition and not to the expected 5-seleno-D-xylopyranose.     

Spontaneous reactions of the irreversible β-D-galactosidase inhibitor 2,6-anhydro-1-deoxy-1-diazo-D-glycero-L-manno-heptitol

2,6-Anhydro-1-deoxy-1-diazo-D-glycero-L-manno-heptitol (2) decomposes in 0.01M methanolic sodium methoxide with a half-life of approx. 18 min. Decomposition in aqueous solution is too rapid for spectrophotometric measurement. Seven products could be identified in methanolic and aqueous reaction mixtures. 2,6-Anhydro-1-deoxy-D-galacto-hept-1-enitol (6), 2,7-anhydro-1-deoxy-β-D-galacto-heptulopyranose (10), and 4-O-vinyl-D-lyxose (12) are products of rapid intramolecular reactions. The major portion consists of the direct solvolysis products 2,6-anhydro-1-O-methyl-D-glycero-L-manno-heptitol (3) and 2,6-anhydro-D-glycero-L-manno-heptitol (5).     

The synthesis of per-C-deuterated D-glucose1

A new, isotopic hydrogen-exchange technique that allows the introduction of deuterium by catalytic exchange with carbon-bound hydrogen was employed for the preparation of per-C-deuterated D-glucose.     

Proton magnetic resonance spectra of D-gluco-oligosaccharides and D-glucans

The p.m.r. spectra of some D-gluco-oligosaccharides and D-glucans in deuterium oxide were studied with respect to the anomeric proton. In (1→2)-linked glucobioses, the effect of change in configuration of the hydroxyl group at C-1 on the chemical shifts of the glycosidic proton is noted. Equilibrium mixtures of (1→2)-linked glucobioses contained more α-anomer than did the other examples, despite the cis configuration of substituents at C-1 and C-2. Some D-glucans were investigated with regard to the degree of branching, although solubility was a limitation.     

Synthesis of D-ristosamine and its derivatives

A convenient preparative route involving eleven steps starting from D-glucose is described for the synthesis of D-ristosamine (15) hydrochloride. Methyl 2-deoxy-β-D-arabino-hexopyranoside, prepared from 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex- 1-enitol, was benzylidenated, and the product mesylated to give methyl 4,6-O-benzylidene-2-deoxy-3-O-methylsulfonyl-β-D-arabino-hexopyranoside. Azidolysis of this compound and subsequent opening of the 1,3-dioxane ring with N-bromosuccinimide gave methyl 3-azido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-βD-ribo-hexopyranoside. Simultaneous reduction of the azido and bromo groups gave a mixture that was benzoylated to give methyl N,O-dibenzoyl-β-D-ristosaminide and then hydrolyzed to 15 hydrochloride (3-amino-2,3,6-trideoxy-D-ribo-hexopyranose hydrochloride).     

Untersuchungen zur modifikation der cellobiose und synthese von methyl-2,6-didesoxy-4-O-(6-desoxy-β-D-glucopyranosyl)-α-D-arabino-hexopyranosid (methyl-4-O-β-D-chinovosyl-α-D-olivosid)

Starting with cellobiosides, several different procedures were employed to prepare 6,6′-dichloro-6,6′-dideoxy, 6,6′-dibromo-6,6′-dideoxy, and 6,6′-dideoxy-6,6′-diiodo derivatives. Reduction with lithium aluminum hydride or nickel boride afforded peracetyl derivatives of methyl, phenyl, and benzyl 6-deoxy-4-O-(6-deoxy-β-D-glucopyranosyl)-β-D-glucopyranoside. Following acetolysis or hydrogenolysis, the glycosyl halide and the corresponding-glycal 40 were prepared. Iodomethoxylation of 40 and subsequent reduction gave the title compound. Alternatively, the halomethoxylation products of cellobial hexaacetate gave, by various procedures, the 2,6,6′-trideoxy-2,6,6′-trihalo derivatives, which, in turn, could be reduced to the title compound. The structures of the derivatives prepared were unequivocally assigned by n.m.r. spectroscopy. The various reaction sequences were compared with respect to the number of steps and the yields obtained.     

Synthesis of derivatives of 3-amino-2,3-dideoxy-l-hexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

The synthesis is described of 3-amino-2,3-dideoxy-l-arabino-hexose (10), methyl 2,3-dideoxy-3-trifluoroacetamido-α-l-lyxo-hexopyranoside (17), methyl 3-amino-2,3-dideoxy-α-l-ribo-hexopyranoside (21), methyl 2,3-dideoxy-3-trifluoroacetamido-α-l-xylo-hexopyranoside (26), and certain derivatives from methyl 4,6-O-benzylidene-2-deoxy-α-l-arabino-hexopyranoside (3). Conversion of 2-deoxy-l-arabino-hexose into 3 by modified, standard procedures, and on a large scale, gave a 75% yield.     

Metabolism of 14C-labelled D-glucose, D-fructose and allitol by Itea plants

The metabolism of D-[1-¹⁴C]glucose, D-[6-¹⁴C]glucose, D-[1-¹⁴C]fructose and D-[6-¹⁴C]fructose by leafy spurs of Itea plants results in rapid incorporation of label into allitol and D-allulose. The patterns of labelling found in the allitol and D-allulose are discussed, a direct interconversion from D-glucose and D-fructose being indicated. Allitol has been found to be an active metabolite in Itea plants.     

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.     

The synthesis of D-xylo-hexos-4-ulose and some derivatives

D-xylo-Hexos-4-ulose has been synthesised, characterised chromatographically, and methyl α-D-xylo-hexopyranosid-4-ulose has been shown to be stable in neutral aqueous solution, contrary to a previous report. Glycosyl phosphate derivatives are also reported.     

D-Galactose 6-phosphate: anomeric distribution and analysis of its synthesis from D-galactose and polyphosphoric acid

D-Galactose 6-phosphate as synthesized by direct phosphorylation of D-galactose with polyphosphoric acid is contaminated with two of its positional isomers. These were separated from D-galactose 6-phosphate and from each other, and identified as D-galactose 3- and 5-phosphate by enzymic, chromatographic, and mass-spectral analysis. The previous misidentification of these isomers as furanose forms of D-galactose 6-phosphate has led to erroneous reports concerning the anomeric distribution of D-galactose 6-phosphate. The anomeric distribution of D-galactose 6-phosphate in a purified preparation was determined by gas-liquid chromatography and ¹³C-n.m.r. spectroscopy to be 32% α-pyranose, 64% β-pyranose, and no more than 4% furanose anomers.     

Two diastereoisomeric 2,3:5,6-di-O-ethylidene-β-D-alloses and related derivatives

Direct condensation of β-D-allose with acetaldehyde in the presence of sulfuric acid formed two of eight possible 2,3:5,6-di-O-ethylidene-D-alloses in overall yields of 84–96%. Conditions of the reaction were varied to favor formation of either isomer. The presence of a furanose ring in both isomers was established by converting the diastereoisomers into 1,4-di-O-acetyl-D-allitol analogs. P.m.r. analysis of the reducing isomers, their 3-deuterio analogs, their 1-O-acetyl derivatives, and the 1,5,6-triacetate of a common hydrolysis product, 2,3-O-ethylidene-D-allose, established the anomeric configuration of D-allose as β-, and the C-2′ atom in the 2,3-O-ethylidene ring as R and as either R or S in the 5,6-O-ethylidene ring.     

The action of thiols on derivatives of D-xylose

The action of thiols on 1,2,3,4-tetra-O-acetyl-β-D-xylopyranose gave 2- and 5-alkylthiopentose dithioacetals and alkyl 1-thio-D-xylopyranosides. On treatment with thiols and trifluoroacetic acid- 3-O-acetyl-1,2-O-isopropylidene-α-D-xylofuranose derivatives rapidly formed 4-O-acetyl-2,3-dialkylthio-D-ribose dithioacetal derivatives, which were in turn converted into 4-O-acetel-3-S-benzyl-2,5-epithio-3-thio-D-ribose (or D-arabinose) dithioacetal.     

Synthesis of 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose,and their conversion into adenine nucleosides

Anti-Markovnikov hydration of the olefinic bond of 5,6-dideoxy-1,2-O-isopropylidene-3-O-p-tolylsulfonyl-α- d-xylo-hex-5-enofuranose (4) and methyl 5,6-dideoxy-2,3-di-O-p-tolylsulfonyl-α-l-arabino-hex-5-enofuranoside (11) by the addition of iodine trifluoroacetate, followed by hydrogenation in the presence of a Raney nickel catalyst in ethanol containing triethylamine, afforded 5-deoxy-1,2-O-ísopropylidene-3-O-p-tolylsulfonyl-α-d-xylo-hexofuranose (6) and methyl 5-deoxy-2,3-di-O-p-tolylsulfonyl-α-d-arabino-hexofuranoside (14), respectively. 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose were prepared from 6 and 14, respectively, by photolytic O-detosylation and acid hydrolysis. Syntheses of 9-(5-deoxy-β-d-xylo-hexofuranosyl)-adenine and 9-(5-deoxy-α-l-arabino-hexofuranosyl)adenine are also described. Application of the sodium naphthalene procedure, for O-detosylation, to 11 is reported in connection with an alternative synthetic route to methyl 5-deoxy-α-l-arabino- hexofuranoside.     

α-D-mannosidase and α-D-galactosidase from protein bodies of Lupinus angustifolius cotyledons

Two forms of p-nitrophenyl α-D-mannosidase and p-nitrophenyl α-D-galactosidase were purified from the protein bodies of mature Lupinus angustifolius seeds. A MW of 300 000 was calculated for both α-mannosidase A and B with K_m = 1.92 and 2.70 mM and activation energies of 10.9 and 10.8 kcal/mol, respectively. α-Galactosidase I and II had MWs of 70800 and 17000 with K_m = 0.282 and 0.556 mM and activation energies 17.7 and 11.5 kcal/mol, respectively. The enzymes had acid pH optima and were inhibited by various metal ions, carbohydrates and glycoproteins. They were able to release free sugar from several putative natural substrate oligosaccharides and the Lupinus storage glycoprotein, α-conglutin.     

Acid-catalysed formation of diacetals from butyraldehyde and certain D-glucitol derivatives

Acid-catalysed dibutyiidenation of 1-deoxy-D-glucitol and 3-O-methyl-D-glucitol yields the 2,4:5,6-diacetals as the main, thermodynamically controlled products, and 2-deoxy-D-arabino-hexitol (i.e., 2-deoxy-D-glucitol) yields the 1,3:4,6-diacetal as the main, thermodynamically controlled product.     

Studies of the dextranase activity of pig-spleen acid α-D-glucosidase

Pig-spleen acid α-D-glucosidase, when purified over 2000-fold, has a molecular weight of ≈ 106,000 and is homogeneous by disc-gel electrophoresis. The enzyme splits reducing, α-D-glucosyl disaccharides and almost completely degrades dextrans that contain (1→3)- and (1→6)-linkages. Dextrans containing (1→2)-linkages are only partially hydrolysed. The kinetic parameters for the acid α-D-glucosidase were obtained by using oligo- and poly-saccharide substrates. Variation of pH, temperature, and inhibitors caused changes in the activity of the acid α-D-glucosidase towards oligo- and poly-saccharide substrates. These results support the earlier suggestion that the enzyme has multiple substrate-binding sites.     

The synthesis and cytotoxic activity of some haloacetamidoalkyl β-D-xylopyranosides

2-Hydroxyethyl 2,3,4-tri-O-acetyl-β-D-xylopyranoside was prepared from 2,3,4-tri-O-acetyl-α-D-xylopyranosyl chloride by the action of 1,2-ethanediol and mercuric acetate. Subsequent mesylation and azide displacement gave 2-azidoethyl 2,3,4-tri-O-acetyl-β-D-xylopyranoside, which was hydrogenated over palladiumon-charcoal and the amine acylated with various haloacetyl halides, to afford 2-(haloacetamido)ethyl 2,3,4-tri-O-acetyl-β-D-xylopyranosides. Deprotection to obtain the free sugars was carried out with 5mM ethanolic sodium ethoxide. 2-(Chloroacetamido)ethyl 2,3,4-tri-O-acetyl-β-D-xylopyranoside was further modified by sequential azide displacement, hydrogenation, and subsequent acylation with various haloacetyl halides to afford 2-[(haloacetamido)acetylamino]ethyl 2,3,4-tri-O-acetyl-β-D-xylopyranosides, which were also deprotected to give the corresponding free sugars. The effects of these haloacetamido analogs on the growth of the melanoma cells in tissue culture was evaluated.