Carbohydrate Chemistry Volume 14

Part I Mono-, Di-, and Tri-saccharides and Their Derivatives

By N. R. Williams

The Royal Society of Chemistry

Copyright © 1983 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-122-7

Contents

1 Introduction, 3,
2 Free Sugars, 4,
3 Glycosides, 12,
4 Ethers and Anhydro-sugars, 36,
5 Acetals, 44,
6 Esters, 49,
7 Halogeno-sugars, 63,
8 Amino-sugars, 71,
9 Miscellaneous Nitrogen Derivatives, 83,
10 Thio-, Seleno-, and Phosphoro-sugars, 92,
11 Deoxy-sugars, 100,
12 Unsaturated Derivatives, 105,
13 Branched-chain Sugars, 115,
14 Dicarbonyl Compounds and their Derivatives, 124,
15 Sugar Acids and Lactones, 127,
16 Inorganic Derivatives, 138,
17 Alditols and Cyclitols, 143,
18 Antibiotics, 152,
19 Nucleosides, 169,
20 N.m.r. Spectroscopy and Contromational Features, 194,
21 Other Physical Methods, 202,
22 Separatory and Analytical Methods, 210,
23 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds from Carbohydrates, 214,
Author Index, 223,

CHAPTER 1

Part I

MONO-, DI-, AND TRI-SACCHARIDES AND THEIR DERIVATIVES

BY B. E. Davison R. J. Ferrier A. C. Richardson N. R. Williams

1 Introduction

Over 1200 references in Part I of this report for 1980 make plain the unceasing interest in the chemistry, and increasingly, the biochemistry of mono- and disaccharides and their derivatives. The large amount of work on glycosides, which was noted last year, has been maintained and there seems no limit to the range of nucleoside analogues which continue to be reported, many of which show interesting biological properties. There is also no sign of an end to the number and diversity of carbohydrate-containing antibiotics being isolated, principally from strains of the remarkable soil actinomycetes, which provide formidable challenges to the synthetic chemist. Carbohydrates, notably glucose, continue to offer attractive chiral templates for the stereoselective synthesis of a wide range of chiral natural products, using reaction sequences that clearly display the ingenuity of the modern carbohydrate chemist. Carbohydrate chemistry is evidently in fine fettle!

An appreciation of William Ward Pigman is contained in the 1980 issue of ‘Advances in Carbohydrate Chemistry and Biochemistry’, which also includes articles on the free-radical reactions of carbohydrates and the synthesis of L-ascorbic acid.

The latest text in the series ‘Methods in Carbohydrate Chemistry’ is devoted to general methods in carbohydrate chemistry, including procedures for separation and analysis of sugars, and the preparation of mono-, oligo-, and polysaccharides and their derivatives.

The final volume of the second edition of ‘The Carbohydrates’ has been published at last, being devoted principally to modified sugars and physical methods of analysis.

Conformational nomenclature recommendations for five- and six-membered ring forms of monosaccharides and their derivatives are contained in a publication from the IUPAC-IUB Joint Commission on biochemical nomenclature.

2 Free Sugars

The radiation chemistry of carbohydrates has been reviewed in Russian, and in English.

A study of D-eryth rose and D-threose in aqueous solution has shown the presence of >1% free aldehydic forms, 10-16% hydrated aldehyde, and the remainder as furanose forms; in the syrup dimeric forms predominate.

A potential-energy function comprising harmonic terms for bond-length and valence-angle distortions with Lennard-Jones and coulomb terms for non-bonded interactions has been developed and shown to be able to reproduce structures of alkanes, alcohols, ethers, and α- and β-D-glucose. Good agreement was obtained for calculated and observed bond lengths and angles and for the free-energy differences between the two anomers.

A journal issue containing reviews on the chemistry of carbohydrates with important food uses has appeared, covering trehalose, sucrose, raffinose and melezitose, maltose, cellobiose, and lactose.

1 Isolation and Synthesis

Two disaccharides isolated from the dried twigs of Sarcostemma brevistigma have been shown to be β-D-digitoxopyranosyl-β-D-digitoxopyranoside and 4-O-(6-deoxy-2-O- methyl-β-D-allopyranosyl)-2,6-dideoxy-D-xylo-hexopyranose. 3-O-Methyl-L-rhamnose has been isolated from hydrolysates of a Rhizobium capsular polysaccharide.

A study of carbohydrates in human erythrocyte membranes during ageing has shown there is a homogeneous decrease in the concentrations of fucose, mannose, galactose, glucose, 2-acetamido-2-deoxy-D-glucose, and -D-galactose during ageing, although the relative proportions do not appear to change D-[U-13C] Galactose and [U-13C]glycerol have been prepared by hydrolysis of [U-13C]-2-hydroxy-1-(hydroxymethyl)ethyl-α-D-galactopyranoside formed by photosynthesis when the marine red alga Gigartina corymbifera was supplied with 13CO2. Photosynthesis has also been exploited in the formation of [U-11C]glucose from H211CO3 by Scenedesmus obtusiusculus. A 50-70% yield was obtained in 0.5 h at 30 °C. A 44% yield of D-[U-14C] arabinose has been obtained by treatment of D-[U-14C]glucose 2-nitrophenylhydrazone with ammoniacal sodium molybdate-hydrogen peroxide mixtures. D-[5-3H]Mannose and L-[5-3H]gulose have been prepared by the route shown in Scheme 1.

The Kiliani reaction with D-arabinose using [13C] cyanide and [13C, 15N] cyanide has been investigated by means of 13C n.m.r. spectroscopy. The reaction was shown to be complex, involving cyanohydrins, amides, lactones, amidines, and an imidate. The reaction, followed over the pH range 5.1-12.5, was shown to produce gluconate : mannonate ratios dependent upon the pH and not upon the presence of metal ions.

An abbreviated synthesis of penta-O-acetyl-α-D-altropyranose, and hence altrose, involves treatment of methyl 2,3-anhydro-4,6-O-benzylidene-α-D-allo-pyranoside with acetic anhydride-sulphuric acid mixtures. The peracetate was obtained in 64% yield.

The use of 4,5-dihydro-2-lithio-5-methyl-1,3,5-dithiazine instead of 2-lithio-1,3-dithian gives better results in the chain extension of sugars, the former being more reactive and the products more readily desulphurized.

Chapter 7 contains a reference to a synthesis of L-idose among many reactions resulting from photobromination of penta-O-benzoyl-β-D-glucopyranose, and the synthesis of pure anhydrous D- and L-gulose via boronate esters of sugar lactones is covered in Chapter 16 (Schemes 1 and 2).

A review in Russian on the synthesis of carbohydrates from formaldehyde has appeared. An investigation of the formose reaction by g.c.-n.m.r. has shown that intermediate glycoaldehyde, glyceraldehyde, and dihydroxyacetone are present as mixtures of monomers, e.g. hydroxycarbonyl compounds, epoxides and hydrates, and dimers such as half and full acetals. Further study of the barium chloride-catalysed formose reaction at pH 12 has shown that the main product forming 33% of the total sugars is the branched pentulose (1). The sugar yield reached a constant value at 70% completion of the reaction, i.e., within 25 min at 60 °C under nitrogen. The presence of fructose as co-catalyst with N,N-diethylethanolamine has been shown to modify the reaction considerably. Use of the catalyst alone yields only pentaerythritol, whereas when fructose was present 2-hydroxymethyl-glycerol was the main product. A stepwise mechanism of autocatalysis has been proposed for the formose reaction in the presence of calcium hydroxide on the basis of kinetic results. Glucose, galactose, xylose, arabinose, and glyceraldehyde dimer have been identified in the product mixture from formaldehyde condensation in the presence of thiazolium ions.

Treatment of 2,3,4,6-tetra-O-methyl-α,β-D-glucopyranose with 30% hydrogen peroxide in the presence of potassium hydroxide yields the products (2)-(7), thought to arise by decomposition of the hydroperoxide (8). Mechanistic schemes were proposed. 23 The formation of reductic acid from methyl β-D-ribo- hexosid-3-ulose by sulphuric acid treatment has been studied by 14C-tracer methods. A caution on the use of labelled-glucose from several manufacturers due to contamination by labelled impurities has appeared. The impurities have been found to bind covalently to proteins and thus simulate non-enzymic glycosylation. This may render some previous results invalid where corroborative evidence is lacking.

2 Physical Measurements

Laser-Raman spectroscopy of D-fructose in aqueous solution has given results for the proportions of furanose and pyranose similar to those from other techniques. A series of studies on the structure of aqueous solutions of D-glucose have been carried out, using electrical conductivity, the dielectric characteristics at 0.01-7.5 M, and proton relaxation times, the latter being dependent on concentration, thus confirming the presence of glucose-water complexes. Data for the absorption frequencies and the rates of ultrasonic transmission in aqueous solutions of D-glucose at various concentrations have been published. The lyoluminescence of sensitized glucose has been reported. The catalytic effects of a series of cations on the decomposition of glucose and xylose have been evaluated. From the study of eighteen different metal ions, it was demonstrated that the trivalent cations were more effective than divalent cations. By means of 13C n.m.r. in 2H2O solution, the open-chain forms of D-fructose, L-sorbose, and D-tagatose have been shown to be present to the extent of 0.80, 0.25, and 0. 30%, respectively.

The kinetics of the thermal reactions of some disaccharides have been determined thermogravimetrically. The rate-determining step is the cleavage of the glycosidic bond, which is followed by the formation of anhydrohexopyranoses by elimination of water. The heats of crystallization of sucrose in the 30-60 °C range vary between 11.6 and 19.5 kJ mol-1. A recent study of the previously reported enhanced solubility of sucrose in water when excess solid phase is present has failed to confirm the claim. It was concluded that the previous measurement was of a transitory occurrence.

The free-radical reactions of carbohydrates as studied by radiation techniques have been reviewed. The nature of the reactions of carbohydrates with hydroxy-radicals and hydrated electrons formed by pulse radiolysis has been investigated. Simple monosaccharides are unreactive towards the solvated electron but readily give unstable species with hydroxy-radicals. Aryl glycosides react readily with both in the manner of nucleophile and electrophile, respectively. Radiolysis of some monosaccharides at >20 mM in formate solution has been studied. The principal reaction is that with xCO2- which arises from the hydroxy-radical interacting with the formate ion: xOH + HCO2- [right arrow] H2O + xCO2-. Therefore, in 100 mM formate, D-fructose gives 1-deoxy-D-arabino-hexulose and 1,3-dideoxy-D-erythro-hexulose, D-ribose gives 2-deoxy-D-ribose and 2-deoxy-D-ribitol, and D-glucose gives 2-deoxy-D-glucose and 2-deoxy-D-glucitol. γ-Radiolysis of carbohydrates in the presence of salts and metal oxides leads to oxidation and degradation, yielding carbonyl compounds, carboxylic acids, and formaldehyde with sulphates and oxides but, interestingly from the point of view of the evolution of life, with nitrates a range of C2C6 amino-acids were formed. The pulse radiolysis of single crystals of sucrose at 6 K yields an absorption spectrum with λmax 450-475 nm attributed to one form of a deeply trapped electron. The decay of this species with increasing temperature was reported.

Using the e.s.r.-ENDOR technique, X-ray irradiation of single crystals of α-D-glucopyranose at 12 and 77 K has been shown to yield four free-radical species: two secondary alkoxy-radicals centred at O-2, a primary hydroxyalkyl radical at C-6, and a secondary hydroxyalkyl radical at C-3.

Determination of the binding constants and their related enthalpy and entropy of activation for D-xylose and a series of n-alkyl β-D-xylopyranosides and their 1-thio-analogues to β-D-xylosidase from Bacillus pumilus has led to the conclusion that the enzyme does not distinguish between alpha- and β-D-xylo-pyranose.

References to the conformations of β-gentiobiose and ketals of D-ribose and L-lyxose are contained in Chapter 20.

3 Isomerizations

The kinetics and mechanism of the acid-catalysed reactions of methylated trioses have been determined and the results were shown to be in good agreement with quantum mechanical calculations of charge distributions in substrates and intermediates. The same group has studied the kinetics and mechanism of acid-base-catalysed enolization of glycolaldehyde and methoxyacetaldehyde by polarography. Deuterium incorporation was used to establish the mechanism. The conditions of Ohno and Ward 480 have been shown to provide more than one pathway for the isomerization of D-glucose in acidic solutions. The conversion of aqueous solutions of D-glucose to D-fructose, D-mannose and D-arabinose by Dowex 1x 2(OH-) required strongly basic resins, with better results being obtained at 30 °C than at 50 °C. The evidence suggested that glucose only reacted when it combined with resin, that a carbonyl group at C-1 is necessary for degradation, and that C-1 is lost as formic acid in forming arabinose. Dioxobis(pentane-2,4-dionato-O,O’)molybdenum(VI) in DMF catalyses epimerization of aldoses at C-2 with no side products. Thus at 50 °C for 5 h D-glucose or D-mannose gave an equilibrium mixture of the former to the latter of 55:45. Under similar conditions [D]-galactose gave 32% D-talose, L-rhamnose gave 55% L-quinovose, and L-arabinose gave 36% L-ribose.

4 Oxidation

Studies on the kinetics of oxidation of D-glucose and D-ribose, and of D-erythrose and DL-glyeraldehyde by chromium(IV) and vanadium(V) in perchloric acid medium have shown that the reaction is first order in oxidant and substrate in each case. Although the reactions are catalysed by acid, the dependence on pH is complex. Free radicals were produced in the reaction. A mechanism was proposed on the basis of the determined activation parameters. The proposal that the formation of free radicals is the rate-determining step has also been made for the vanadium(V) oxidation of L-arabinose. Similar dependencies on concentrations of substrate and oxidant and on pH were reported. The kinetics of oxidation of D-galactose and D-mannose by mercury(I), mercury(II), and silver nitrates at 100 °C have been determined, and the activation energy found to be in the range 80-100 kJ mol-1. The principal products were the corresponding aldonic acids. An investigation of the kinetics of oxidation of maltose and cellobiose by Nessler’s reagent [mercury(II) iodide and sodium hydroxide] has shown that the rates are independent of initial mercury(II) concentration, first order in sugar concentration, and retarded by increasing iodide ion concentration. A mechanism involving intermediate enediols with [HgI3]- as the reacting species was proposed.

5 Other Reactions

The thermolysis of sucrose in DMSO has been shown to yield a fructofuranosyl carbonium ion and α-D-glucose, which subsequently anomerizes. If the latter is generated in the presence of benzyl alcohol, benzyl a- and β-fructofuranosides result. The carbonium ion was thought to be the precursor for the formation of 2,6-anhydrofructofuranose in thermolysis reactions of sucrose.

An examination of the role of anthraquinone in alkaline wood-pulping processes has been carried out using cellobiose, glucose, and glycoaldehyde as model substrates. Each gave a wide range of acid products.

The biosynthetic pathway for the incorporation of glucose into cellulose has been studied by using D-[1-13C]glucose, D-[6-13C]glucose, and D-[U-13C]glucose in admixture with unlabelled glucose as substrates for Acetobacter xylinium, and detecting the presence of the label in the cellulose hydrolysate by 13C n. m. r.

The pH profile for the mutarotation of 6-thio-D-fructose has been determined. The general conclusion was reached that all sugars with sulphur-containing rings show base-catalysed mutarotations several orders of magnitude faster than ring-opening.

3 Glycosides

1 O-Glycosides

A review has appeared on the occurrence of the α-D-galactopyranosidic linkage in the plant kingdom, covering sucrose, alditol, and lipid derivatives. Two reviews published in Japanese have covered recent advances in glycosidation methods (glycosyl halides, 1,2-orthoesters, glycosyl esters, and glycal derivatives as glycosylating agents), and the synthesis of oligosaccharide blood-group determinants [Lea, A, B, H (type I and II)], with particular reference to (i) efficient α-glucosylation, (ii) use of protecting groups, (iii) fucose derivatives, and (iv) common derivatives used as synthetic intermediates.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 14 by N. R. Williams. Copyright © 1983 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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