Synthesis and some reactions of 3,5-di-O-methyl-d-glucose and -fructose

Hydrolysis of 1,2-O-isopropylidene-3,5-di-O-methyl-α-d-glucofuranose by strong acid yielded 3,5-di-O-methyl-d-glucofuranose (6) and its 1,6-anhydride (10). The mechanism of the reaction giving 10 is discussed. On treatment with a catalytic amount of sodium methoxide, 1,2,6-tri-O-acetyl-3,5-di-O-methyl-d-glucofuranose (8) gives the 6-O-acetyl derivative, whereas complete deacetylation, and subsequent isomerization to the d-fructose derivative 16, takes place in the presence of 0.1m sodium methoxide. The structure of 16 was proved both chemically and spectroscopically. Reduction of 6 or 8 with a borohydride afforded 3,5-di-O-methyl-d-glucitol.²     

The synthesis of 1,2:5,6-di-O-isopropylidene-d-mannitol: a comparative study

Three different methods of acetonation of d-mannitol using (a) acetone and zinc chloride, (b), 2,2-dimethoxypropane, 1,2-dimethoxyethane, and tin(II) chloride, and (c) 2-methoxypropene, N,N-dimethylformamide, and p-toluenesulfonic acid were studied in detail and compared, using gas-liquid chromatographic techniques. In each reaction, isomeric diacetals are formed, but method a gives the 1,2:5,6-diacetal in the highest yield (63%). Methods b and c give a more complex mixture of acetals than proposed in the literature, and both methods are less economical than a. A new 1,2:3,6:4,5-tri-O-isopropylidene-d-mannitol could be separated, and its graded hydrolysis was compared to that of the 1,2:3,4:5,6-triacetal.     

Synthesis of 6-deoxy-5-thio-d-glucose

Three routes were investigated for the conversion of d-glucose into the title compound. In the first approach, reduction of the 5,6-thürane ring of 5,6-dideoxy-5,6-epithio-1,2-O-isopropylidene α-d-glucofuranose (17) as well as that of its 3-O-allyl derivative (13) with lithium aluminium hydride was investigated; 17 afforded the corresponding 6-deoxy derivative besides di-, tri-, and poly-mers, whereas only polymers were formed from 13. In the second approach, the oxirane ring of was reduced by sodium borohydride and the resulting 6-deoxy derivative was converted into the 5-thiobenzoate; the corresponding hex-4-enofuranose was formed as a byproduct. In the third approach partial mesylation of methyl 5-thio-α-d-glucopyranoside was attempted, but the 6-mesylate 27 could be isolated only in modest yield (28%) together with rearranged 2,5-thioanhydromannofuranoside derivatives. The mechanism of this rearrangement is discussed in detail. The 6-mesylate 27 was converted via the 6-iodo derivative into the title compound.     

Reaction of methyl β-d-glycero-l-manno-heptopyranoside with cyclohexanone: Synthesis of the 4- and 6-methyl ethers of d-glycero-l-manno-heptitol

Acid-catalysed condensation of methyl β-d-glycero-l-manno-heptopyranoside with cyclohexanone yielded an approximately 3:1 mixture of the 2,3:6,7- and 2,3:4,7-di-O-cyclohexylideneheptosides (1 and 2), which could be separated either as their benzoates (3 and 4) or as their methyl ethers (5 and 6). The latter compounds afforded the 4- and 6-methyl ethers (7 and 8) of d-glycero-l-manno-heptitol.     

Acetalation of d-glucitol: 2,3:5,6-Di-O-isopropylidene-d-glucitol

The reaction of d-glucitol with acetone-zinc chloride gave a mixture of isopropylidene derivatives, from which the 2,3:5,6-diacetal (12) could be separated as its 1,4-dimesylate (13) or 1,4-ditosylate (14). The structure of 12 was proved by converting 14, via the 1-mono-iodide, into the known 1-deoxy-d-glucitol, and by mass-spectrometric investigation of the 1-deoxy-4-O-methyl diacetal. The terminally situated acetal group in 12 can be selectively hydrolyzed, and, on treatment with base, the 5,6-dihydroxy derivative obtained gives a d-galactitol 4,5-epoxide derivative.     

Syntheses of 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-d-glucopyranose (n-acetylmaltosamine) and 2-acetamido-2-deoxy-4-O-β-d-glucopyranosyl-α-d-glucopyranose

Condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-benzyl-1-O-(N-methyl)acetimidoyl-β-D-glucopyranose gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside which was catalytically hydrogenolysed to crystalline 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranose (N-acetylmaltosamine). In an alternative route, the aforementioned imidate was condensed with 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose, and the resulting disaccharide was catalytically hydrogenolysed, acetylated, and acetolysed to give 2-acetamido-1,3,6-tri-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-α-D-glucopyranose Deacetylation gave N-acetylmaltosamine. The synthesis of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose involved condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of mercuric bromide, followed by deacetylation and catalytic hydrogenolysis of the condensation product.     

The crystal structure of d-glucose 6-(sodium hydrogen-phosphate)

The title compound, when recrystallised from water, is monoclinic, space group P2₁, with a = 5.774(4), b = 7.189(5), c = 12.69(1) Å, β = 106.66(5)°, and Z = 2. The crystal structure was determined from three-dimensional X-ray diffraction data taken on an automatic diffractometer with CuKα, and refined by least-squares techniques to R = 0.034 for 977 reflexions. The pyranose ring adopts the ⁴C₁ conformation. The conformation about the exocyclic C-5-C-6 bond is gauche-trans [the torsion angles O-6-C-6-C-5-O-5 and O-6-C-6-C-5-C-4 are 64.2(8) and ?175.6(7)°, respectively], which is significantly different from the gauche-gauche geometry in d-glucose 6-(barium phosphate). The phosphate ester bond, P-O-6, is 1.584(3) Å. All of the oxygen-bonded hydrogen atoms are involved in intermolecular hydrogen-bonds.     

Studies on aroyl- and aryl-hydrazide derivatives from d-glycero-d-gulo-heptono-1,4-lactone

A series of aroyl- and aryl-hydrazide derivatives was prepared from d-glycero-d-gulo-heptono-1,4-lactone (1). The reactivity of the NH proton in these hydrazides, in terms of their dissociation constants (pK_a), was determined from their electronic spectra, and correlated to the Hammett σ values of the substituents. Comparable reactivities of the NH protons for the compounds, and the effect of the substituent, were studied by n.m.r. spectroscopy. Decomposition of the aroylhydrazides with copper(II) sulfate or nitrous acid resulted in the regeneration of 1.     

Nature of the uptake of d-galactose, d-glucose and α-methyl-d-glucoside by Saccharomyces cerevisiae

Both glucose-grown baker's yeast after induction and galactose-grown yeast appear to take up d-galactose by a system not requiring phosphorylation and only up to a diffusion equilibrium, as shown by pulse labelling, sampling at very short intervals and chromatographic analysis of extracts. Part of the sugar taken up is transformed into trehalose which is present in substantially greater amounts in cells than the transported sugar itself. The effect of 2,4-dinitrophenol and of iodoacetamide, as well as the nature of the efflux of sugars from preloaded cells, support the results. d-Glucose and α-methylglucoside are also taken up without phosphorylation.     

Effects of various conditions on the alkaline degradation of d-fructose and d-glucose

Dilute solutions of d-fructose and d-glucose undergo alkaline degradation, and, at temperatures in the range of 30–70°, almost two moles of alkali are consumed per mole of the carbohydrate. The degradation is partly guided by the dielectric constant of the medium; such additives as acetone and urea have specific effects where the reactions are not essentially guided by the medium dielectric. Acetone and urea presumably form complexes with the carbohydrates; this is revealed for the former by the formation of a dark red solution having a spectral band at 320 nm, like that observed earlier in the presence of ethylenediamine.     

Specific d-glucose transport in sarcolemma vesicles

The sarcolemmal fraction prepared from rat skeletal muscle consists of osmotically active vesicles that accumulate d-glucose in preference to l-glucose, apparently by facilitated diffusion into intravesicular space. Stereospecific d-glucose uptake by these vesicles is a saturable process, inhibited by phloridzin, by cytochalasin B, and by certain sugars, and enhanced by counterflow. An additional leak pathway permits entry of both d- and l-glucose into the vesicles.Stereospecific d-glucose transport by sarcolemmal vesicles is enhanced to a small extent by insulin, provided the hormone is administered prior to cell disruption. In membranes prepared from insulin-pretreated muscle, Ca²⁺ produces a small further enhancement. Local anesthetics preferentially inhibit stereospecific d-glucose transport. Apparent uptake of both d- and l-glucose is greater when vesicles are suspended in salt solutions rather than sucrose, an effect attributed to increased functional vesicular volume.     

A convenient synthesis of p-nitrophenyl 2-deoxy-2-(thio-acetamido)-β-d-glucopyranoside, -galactopyranoside,and their 1-thio analogs as inhibitors of 2-acetamido-2-deoxy-β-d-glucosidase

The acetamido group of p-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside, -β-d-galactopyranoside, and their 1-thio analogs was modified by replacement of the amide-carbonyl oxygen atom with sulfur by treatment of their fully acetylated derivatives with phosphorus pentasulfide in pyridine. The resulting p-nitrophenyl 2-deoxy-2-thioacetamido-β-d-hexopyranoside triacetates were O-deacetylated with catalytic amounts of sodium methoxide in methanol to obtain p-nitrophenyl 2-deoxy-2-thioacetamido-β-d-glucopyranoside, -β-d-galactopyranoside, and their 1-thio analogs. These derivatives inhibited 2-acetamido-2-deoxy-β-d-glucosidase from Turbatrix aceti to various extents. Also obtained in significant yields in the aforementioned reaction with phosphorus pentasulfide in pyridine were the two hitherto unreported thiazolines, namely, 2-methyl(2-acetamido-3,4,6-tri-O-acetyl-α-d-glucopyrano)[2′,1′:4,5]-2-thiazoline and 2-methyl(2-acetamido-3,4,6-tri-O-acetyl-α-d-galactopyrano)[2′,1′:4,5]-2-thiazoline.     

Synthesis and growth regulator activity of fatty acyl derivatives of d-glucose and d-galactose

In an attempt to gain information about one or more components of the brassin complex, fatty acid esters of d-glucose and d-galactose were prepared and tested for growth regulator activity in a bean hypocotyl bioassay. 4-O-Acyl-d-glucoses and, perhaps, 1-O-acyl- d-galactoses had a similar qualitative activity to that of the brassin complex. 3-O-Acyl- d-galactoses inhibited elongation of bean hypocotyls and stimulated rooting. 3- And 6-O- acyl-d-glucoses both stimulated and inhibited elongation, depending on the source of fatty acids; in both cases, stimulation was observed when safflower oil was used as the source of fatty acids and inhibition was observed when peanut oil was used as the source of fatty acids. Fatty alkyl β-d-galactopyranosides were inactive.     

Rapid and sensitive,colorimetric determination of the anomers of d-glucose with d-glucose oxidase,peroxidase, and mutarotase

A modification, utilising mutarotase, of an enzymic, colorimetric system for determining d-glucose with d-glucose oxidase, peroxidase, and ABTS was satisfactory for the assay of the anomers of d-glucose in aqueous solution. The time required for a single assay is ≈ 10 min, and the lower limit is 0.4 μg of d-glucose. The method is applicable to the anomer analysis of d-glucose released by enzymic hydrolysis of d-glucosides.     

Aminodeoxynucleosides: synthesis and conformational studies of 7-(4-amino-4-deoxy-α-d-talopyranosyl)theophylline and 7-(6-amino-6-deoxy-α-d-mannopyranosyl)theophylline,and preparation of nucleoside-amino acid derivatives

The synthesis of new aminodeoxy and amino acid nucleosides of talose and mannose is described. The unusual conformation of these hexosylpurines revealed by n.m.r. spectroscopy is reported, as well as the unexpected results of some substitution reactions.     

The effect of areneboronic acids on the alkaline conversion of d-glucose into d-fructose

Benzeneboronic acid, 4-methoxybenzeneboronic acid, 3-nitrobenzeneboronic acid, and sulphonated benzeneboronic acid have been used to displace the pseudo-equilibria established in aqueous alkali between d-glucose, d-fructose, and d-mannose to give greatly increased yields of d-fructose. The effect of reaction temperature, pH, overall concentration, and molar ratio of acid:sugar on the yield of d-fructose has been investigated by using an automated assay for d-fructose.     

Electrokinetic studies of the testosterone-aqueous d-glucose interface

Electro-osmosis and streaming-potential measurements were made across a testosterone-plug membrane, using water and aqueous solutions of d-glucose as permeants. The electrophoretic velocity of testosterone particles dispersed in these solutions was also measured, experiments being confined to the range where linear flux-force relationships hold. Phenomenological coefficients were evaluated by using these linear relations, and the results analyzed inthe light of the thermodynamics of irreversible processes. Saxen's relationship holds between electro-osmosis and streaming potential. Concentration dependence of the various phenomenological coefficients was also examined. Cross-phenomenological coefficients were found to decrease with increase in the concentration of d-glucose solutions. The results are explained on the basis of strong hydrogen-bonding between d-glucose and the surrounding water molecules. Such membrane parameters as pore size, average number of pores, and the membrane constant were evaluated. Electro-osmotic and electrophoretic data were used to estimate the zeta potential, in order to characterize the membrane-permeant interface. The dependence of the zeta potential on the concentration was also examined.     

Quantitation of l-glycero-d-manno-heptose and 3-deoxy-d-manno-octulosonic acid in rough core lipopolysaccharides by partition chromatography

A partition chromatographic procedure utilizing a cationic exchange resin column in the Li⁺ form and 90% ethanol as the mobile phase was employed to quantify 3-deoxy-d-manno-octulosonic acid (KDO) and l-glycero-d-manno-heptose in the lipopolysaccharides (LPS) of R_e and R_dP^? rough mutants of Salmonella minnesota. In a standard mixture of monosaccharides, KDO eluted shortly after the void volume and heptose eluted after the neutral hexoses. Mild acid treatment of either the R_e or R_dP^? LPS with 0.16 n methanesulfonic acid in the presence of Dowex 50-X8 resin (H⁺ form) released more than 80% of the KDO residues within 15 min. The heptose of the R_dP^? LPS, first detected after 90 min of hydrolysis, increased gradually to a maximum level at 12 h. A secondary gradual increase in KDO became apparent during the heptose release. The weight contents of these two monosaccharides based upon aheir maximum values detected during hydrolysis were 20.3 ± 0.6% KDO, for the R_e LPS, and 13.8 ± 0.4% KDO and 12.0 ± 0.4% heptose, for the R_dP^? LPS. The relationship between the kinetics of release of KDO and heptose and the nature of the linkages involving these two monosaccharides are discussed.     

2,5-anhydro-d-hexitols: syntheses of 2,5-anhydro-d-altritol and 2,5-anhydro-d-iditol

2,5-Anhydro-d-altritol (2a) and the previously-unknown 2,5-anhydro-d-iditol (3a) have been prepared from 2,5-anhydro-d-mannitol (1a). The preparation of 3a from the intermediate epoxide 7b is particularly sensitive to pH, and a mechanism is proposed to explain this. Attention is drawn to the limitations of the trifluoroperacetic acid-disodium hydrogenphosphate procedure for the epoxidation of alkenes of diminished reactivity.