Carbohydrate Chemistry Volume 21 Part I

Monosaccharides, Disaccharides, and Specific Oligosaccharides

By N. R. Williams

The Royal Society of Chemistry

Copyright © 1989 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-232-3

Contents

Chapter 1 Introduction and General Aspects, 1,
Chapter 2 Free Sugars, 2,
Chapter 3 Glycosides and Disaccharides, 14,
Chapter 4 Oligosaccharides, 41,
Chapter 5 Ethers and Anhydro-sugars, 48,
Chapter 6 Acetal, 57,
Chapter 7 Esters, 61,
Chapter 8 Halogeno-sugars, 75,
Chapter 9 Amino-sugars, 82,
Chapter 10 Miscellaneous Nitrogen Derivatives, 100,
Chapter 11 Thio-and Seleno-sugars, 112,
Chapter 12 Deoxy-sugars, 119,
Chapter 13 Unsaturated Derivatives, 127,
Chapter 14 Branched-chain Sugars, 137,
Chapter 15 Aldosuloses, Dialdoses, and Diuloses, 150,
Chapter 16 Sugar Acids and Lactones, 154,
Chapter 17 Inorganic Derivatives, 167,
Chapter 18 Alditols and Cyclitols, 172,
Chapter 19 Antibiotics, 187,
Chapter 20 Nucleosides, 201,
Chapter 21 N.M.R. Spectroscopy and Conformational Features, 225,
Chapter 22 Other Physical Methods, 234,
Chapter 23 Separatory and Analytical Methods, 244,
Chapter 24 Synthesis of Enantiomerically Pure Noncarbohydrate Compounds, 256,
Author Index, 271,

CHAPTER 1

Introduction and General Aspects

We hope that the following chapters provide a fair summary of the large amount of carbohydrate chemistry published in 1987, and give an indication of the wide range of compounds reported and studied during the year. The report covers monosaccharides, disaccharides, and specific oligosaccharides (as defined in Chapter 4). As usual, the most extensive chapters cover glycosides and nucleosides, but several other chapters contain a large number of references, and over 1500 references altogether demonstrate the interest in this area of chemistry. The report reflects a particular surge of interest in C-glycosides in Chapter 3 and in inositol phosphates in Chapter 18.

The lack of a precise definition of a carbohydrate has led to somewhat arbitrary decisions as to whether border-line cases merit inclusion in our survey; we have tried to assess likely interest to carbohydrate chemists, or whether significant carbohydrate chemistry is discussed in work focussed as much if not more on aglycone units. We apologize if our judgement does not always meet with your approval.

Reviews of a more general nature not covered elsewhere in this report include a review on the evolution of a general strategy for the stereoselective construction of polyoxygenated natural products, and a review of some miscellaneous topics involving synthetic reactions of carbohydrates, including syntheses of aminosugars, deoxysugars, glycosides, and the Ferrier ring synthesis.

CHAPTER 2

Free Sugars

Reviews covering the structural determination of carbohydrates by chemical and spectroscopic means, the uses of lithium aluminium hydride-aluminiuu chloride and acidic sodium cyanoborohydride in the reduction of carbohydrates and their derivatives, and chemical and biological preparations of D-ribose have appeared.

The hydrogenolysis of U-glucose in aqueous and non-aqueous solution using palladium, rhodium or ruthenium catalysts supported on carbon has been investigated. Of these, only the ruthenium catalyst at 200 °C and a pressure of 50 bar allowed conversion of glucose into iaethanol.

1. Theoretical Aspects

Calculations of the electronic structures of a series of carbo-hydrates using the CNDO/2 method have produced linear relationships between 13C-n.m.r. chemical shifts and the atomic charges for the α- and β-D-glucose, α- and β-D-galactose and β-L-arabinose systems. Model systems, treated by the RHF/STO-3G method, have been used to evaluate the anomeric and Δ2 effects in simple and 1-O-methylpyrano-sides and hence derive their conformational and anomeric energies. 1,1-Dihydroxyethane and 1,1-dimethoxyethane were chosen as model systems for the anomeric effect while the Δ2 effect was investigated using 1,1, 2-trihydroxyethane and 2,2-dirnethoxyethanol. A theoretical study of the structure of D-glucopyranose in eleven solvents by a PCILO quantum mechanical method has been carried out. The stability of the individual conformers was compared using a method in which the total energy is divided into the energy of an isolated molecule and the solvation energy. The influence of the solvent on rotation of the pendant groups and on the stability of anomers was investigated; the results were found to be in good agreement with experiment. The method was further extended to the anomeric pairs of all eight 0-hexopyranoses. The theoretical basis of distinguishing the configuration of the aldoses has been described using the concept of rotational symmetry. A comprehensive treatment of aldose configurations was developed in symmetry terms and presented as dichotomous trees.

A new kinetic model for the alkaline isomerization and degradation of monosaccharides has been presented. Computer simulations using the model fit the experimentel data and allow determination of all relevant rate constants. The rate limiting step appears to be enolization for both isoraerization and degradation. The mechanism of redox reactions between lead hydroxide and 3-O-methyl-U-glucose nas been studied by quantum mechanical calculations. The calculations snow that there is a redistribution of electron density in both systeus which favours the formation of a carboxyl group in the C(1)-C(3) part of the aldose.

2. Synthesis

Peracetylated sugars treated with tributyltin methoxide gave products selectively deacetylated at the anomeric position (Scheme 1). Equatorial anomers were deprotected more rapidly and uore selectively than their axial- counterparts. Anodic electrolysis has been used to deprotect aldose dithioacetals in good yield. Other acetals were found to be stable to the cohditions. Thus 2, 3, 4, 5, 6-penta-O-acetyl-D-galactose diethyldithioacetal gave 2, 3, 4, 5, 6-penta-Q-acetyl-D-galactose in 65% yield; other examples quoted gave the free sugar in higher yields. D-Mannitol has been converted into D-mannose by the photolysis of the azide (1) as shown in Scheme 2. Some [1-13aldoses have been synthesized by conventional means and used to study their 75MHz 13C-n.m.r. spectra. A convenient method for preparing pure [11glucose by photosynthesis from 11CO 2 using spinach leaf and hydrolysis of the labelled sucrose produced has been described. References to the preparation of [1-13C]-enriched 5-deoxypentoses and 5-O-methylpentoses are made in Chapters 5 and 12.

Sophorose has been easily prepared on an industrial scale from stevioside by partial acid hydrolysis.

The formose reaction, carried out at room temperature in the presence of calcium hydroxide, has been studied. The effects of the presence of oxygen and reducing sugars on the formose reaction using calcium hydroxide-methylene glycol have been described. The induction period was found to be shortened by reducing sugars but increased by oxygen, although the rate after induction remained the same; large quantities of added reducing sugar decreased the conversion rate. The progress of the reaction could be followed by measuring the pressure above the reaction mixture. The same workers have carried out a detailed study of the pressure-volume changes in this reaction; the formation of the complex between calcium hydroxide and methylene glycol was accompanied by a volume contraction, which was followed by two stages of volume increase, corresponding to the induction period and the period during which sugars are formed.

The isomerization of monosaccharides by aqueous potassium hydroxide under nitrogen has been monitored by liquid chrolnatography on cation(Pb2+ ) exchange and reverse phase columns. The simple epimerization reaction of pentoses and hexoses accounts for about 90%, of the saccharides found in the solution after one week. ‘The remaining sugars were formed either by fragmentation or recombination; e.g., glucose and sorbose are found in the isonerization mixtures of pentoses. The aldol reaction responsible for the formation of hexoses from glyceraldehyde at pH 11.5 was found to be fast, thus accounting for the rapid fragmentation and recombination observed.

The previously reported rapid interconversion of D-glucose and D—mannose by nickel(II) and N, N, N’ -trimothylethylenediamine (see Vol. 19, p.162) has been extended to other metal ions (cobalt(II), calcium, and strontium) and N, N, N’,N’-tetramethylethylenediamine-(tetmen). The best system was found to be nickel(II)-tetmen. The epimerization reaction was shown to involve a 1,2-carbon shift, i.e., a skeletal rearrangement, by means of 13C-n.m.r. of the products of the nickel( II )- N, N, N’-trimethylenediamine treatment of D-[1-13C]glucose when the product was shown to be D-[2-13C]mannose. Similar rearrangements were shown to occur in reactions with alkaline earth or rare earth metal ions and monoamines. Molybdate catalyzed epimerization of D-erythro-L-manno-octose gave a mixture of D-erythro-L-gluco-octose and the starting sugar with the former predominating.

The metal-ion catalyzed photoreactions of sugars which result in cleavage of carbon-carbon bonds have been reviewed.

Chain extension using an insertion reaction of dichloromethyllithium or dibromomethyllithium with a cyclic chiral boronate derivative, (S)-pinanedioll ( benzyloxy )methyl]boronate (2), has been used in a synthesis of L-ribose in 13% overall yield (Scheme 3). A new synthetic equivalent (3) of the glycolaldehyde anion has been used for the two carbon chain extension of aldehydes. Thus L-ribose was synthesized from 2,3-O-cyclohexylidene-L-glyceraldehyde and a boronate (3) by the addition shown in Scheme 4. Diaddition and higher addition reactions to yield polymers is alleviated by using a polymer-supported reagent as shown in the Scheme. The main product gave L-ribose after deprotection. The observation that the proportions

of diastereoisomers formed in the condensation of glycolaldehyde with DL-glyceraldehyde and in the triose aldol condensation vary little with changes in the metal hydroxide catalysis has been interpreted as evidence for a pericyclic transition state involving cisenediolate attack on the aldehyde. The earlier work on base-catalyzed condensation of glycolaldehyde and hydroxyketones (see Vol. 18, p.7) has been extended to the reaction of the racemic tetrulose (4) which gives D,L-lyxo-3-hexulose (5) as the major product and its C-2 epimer as the minor one. The former was isolated as its 1,2 : 3,4-di-O-isopropylidene derivative (6).

Ketoses have been prepared using transketolase catalysis. The enzyme, isolated from Saccharomyces cerevisiae (baker’s yeast) or from spinach leaf was investigated for substrate specificity and it was shown that it was not necessary for the ketose to be phosphorylated. The general biosynthetic condensation shown in Scheme 5 was used in the preparation of L-erythrulose from glycolaldehyde, D-xylulose from D- or D,L-glyceraldehyde, and 5-deoxy-D-xylulose from D, L-lactaldehyde. L-Glyceraldehyde was not active as a substrate.

A review on total synthesis of higher honosaccharides concentrates mainly on the author’s work on the hetero-Diels Alder reaction between an aldehyde and an electron-rich diene. Vinyltin derivatives (7) of simple monosaccharides, prepared as shown in Scheme 6, react with butyllithium to give the corresponding vinyl-lithium compound, which may be reacted with aldehydosugars to give the higher sugars.

Osmylation of higher octenoses, previously reported (see Vol. 19, p.6; Vol. 20, p.6), has been used to synthesize β-L-threo-D-gluco- and -D-manno-octopyranoside. Inversions at C4 and C5 of hne heptose derivative (8) using sodium methoxide gave rise to 2, 3:6, 7-di-O-isopropylidene-β-L-glycero-L-allo-heptofuranoside (9) via the an-hydrosugar (10) as shown in Scheme 7.

Carbon-labelled hidher sugar phosphates of the pentose pathway are referred to in Chapter 7.

3. Physical Measurements

Enthalpies of combustion of D-ribose and 2-deoxy-D-ribose have been measured by bomb calorimetry. Ultrasonic, volumetric and viscometric measurements have been performed on aqueous solutions of D-glucose and D-mannose at 20° and 30 °C. These measureinents were used to evaluate important ultrasonic and thermodynamic parameters including apparent and 2artial molal volume, apparent and partial molal compressibility, viscosity B-coefficients of the Jones-Dole equation, and changes in free energy, entropy, and enthalpy on dissolution. The parameters were used to explain the predominant solute-solvent interactions.

Rate constants for the tautomerization of 5-hydroxypentanal have been determined by line shape 13C-n.m.r. analysis. The muta-rotation of U-fructose to a five component equilibrium mixture of the two pyranose, two furanose and the open chain forms has been re-examined by g.c. and g.c.-m.s. of pertrimethyisilylated samples, the β-pyranose to β-furanose equilibrium being the major contributor. The mutarotation of β-glucose in some mammalian body fluids has been measured using β-glucose oxidase-mutarotase and polarimetry. The mutarotation was more rapid than in distilled water in many cases.

All six tautomers of D-glucose in aqueous solutions have been detected and quantified using high resolution 13Cn.m.r. on D-[1-13 C]glucose. 13C-n.m.r. has also been used to determine the proportions of pyranose and furanose forms in aqueous solutions of thirteen monosaccharides. Equilibrium tautomers of allose, altrose, gulose, idose, and talose have been analyzed as their trimethylsilyl ethers by capillary g.c. Aldopentoses were also examined. G.c.-m.s. and n.m.r. were used to identify the components. The proportions of furanose and pyrariose ring forms in DMSO solutions of glucose, galactose, arabinose and 3-O-(α- and α-D-galactopyranosyl)-D- and -L-arabinose have been determined by nakamori methylation and g.c.-m.s. analysis of their derived methylated alditol acetates. The values would appear to represent those obtaining under the conditions of the methylation procedure. N.m.r. studies support the idea that D-fructose exists mainly as the β-furanose in DMSO due in part to the OH-I to OH-4 hydrogen bond, as previously suggested (see Vol. 19, p.9). However, an important factor, as the authors suggest, is the influence of the medium on the free energy of the [betas]-pyranose form, which predominates in aqueous solution; changes in tautomeric composition in mixtures of DMSO and water indicate that specific solvation by water is the main factor in stabilization of the β-pyranose form. Trenalulose (1-O-α-D-glucopyranosyl-D-fructose), isolated by preparative reversed-phase HPLC from the crystallization liquors of isomaltulose, has been shown by 13C-n.m.r. to exist as a 2:1 mixture of the β-fructopyranoid and β-fructo-furanoid forms in water.

An ingenious examination of the ability of the anomers of the eight 2-aldohex-oses to form hydrogen bonds to water has allowed a rationalization of their α:β ratios ill aqueous solution. By means of a kinetic study of standard amide hydrolyses in aqueous carbohydrate solution the carbohydrate-solvent interactions causing inhibitory kinetic effects have been evaluated. Whilst dilute solutions of several free sugars show almost ideal thermodynamic behaviour, other affects are attributed to sugar-induced alterations in the three-dimensional H-bonded structure of water.

An in situ e.s.r. study of the formation and structure of radicals from D-ribose and 2-deoxy-D-ribose has shown that radicals are formed at C-1, C-2, and C-3 by hydrogen abstraction followed by regioselective α,β-water elimination, thus giving 2-deoxyribono-lactonyl, 1-deoxypentopyranos-2-ulos-1-yl and 4-deoxypentopyranos-3-ulos-4-yl.

Construction of an apparatus for measuring electrocapiliary curves of the mercury-electrolyte interface based on the maximum bubble pressure technique has allowed the study of the absorption of D-xylose, D-ribose, and sucrose at the mercury-0.7953M sodium fluoride interface.

[??]-Irradiation of α-D-glucose at 77-415K has been investigated by e.s.r. analysis, which showed that the chain reaction was propagated from initially formed radicals by decomposition to sugar acids and by dehydration to yield secondary radicals.

4. Oxidation

The kinetics of the oxidation of D-galactose, D-glucose, D-mannose, D-fructose, L-sorbose, L-arabinose, D-ribose and D-xylose with cerium(IV) in perchloric acid showed that two complexes were formed in each case. The first forms in a pre-equilibrium reaction during mixing acid is partly oxidized via Michaelis-Menton Kinetics and partly dissociated to the second. The latter is oxidized more slowly than the former. The pseudo first order rate constant in 1.OM perchloric acid was almost constant over the range of sugar concentrations 0.1M to 1.0M, from which it was concluded that practically all the cerium(IV) was complexed. Kinetic parameters for the oxidation of D-lyxose by iron(III) and cerium(IV) sulphates have been determined. Both reactions are first order in oxidant, and various organic acids are produced. Thallium(III) in a twelve molar equivalent oxidizes D-fructose completely to carbon dioxide. Formaldehyde and formic acid are formed as intermediate products, the rate of oxidation being strongly inhibited by the presence of chloride or acetate ions. The Kinetics and mechanism of oxidation of D-fructose by copper-pyridine complex in excess pyridine have been studied spectrophotometrically. The observation that the rate of oxidation was equal to the rate of enolization led to the proposal that the reaction species was the enediolate anion, Ruthenium(III) catalyzed oxidation of aldoses by DBS has been studied in aqueous acetic acid in the presence of Mercury(II) acetate and sulphuric acid. The reaction was first order in BBS but the order in aldose concentration changed from one to fractional in the presence of the catalysts. It was suggested tnat the reactive species is the α-anomer in the D-series; D-arabinose, D-xylose, D-galactose, D-mannose, and D-glucose were examined, the rate of oxidation decreasing in the order given. Oxidation of D-xylose by potassium bromate in dilute sulphuric acid to give D-xylonic acid has been studied kinetically, and the thermodynamic constants determined. The changes in ascorbic acid induced by oxygen have been examined. It was found that the rate of oxidation increased with pH, decreased in the presence of glucose, was slightly increased by maltose, while the presence of tartaric acid caused little change. Oxidation of ascorbic acid by molecular oxygen catalyzed by copper(II) and by copper(II) glycine peptides has been studied. The pertechnate ion oxidizes ascorbic acid to give a red species which comprises technetium(V)-dehydroascorbate complex. Kinetics of the reaction were measured and Arrhenius parameters were obtained.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 21 Part I by N. R. Williams. Copyright © 1989 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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