Carbohydrate Chemistry Volume 19

Part I Monosaccharides, Disaccharides, and Specific Oligosaccharides

By N. R. Williams

The Royal Society of Chemistry

Copyright © 1987 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-222-4

Contents

Chapter 1 Introduction, 1,
Chapter 2 Free Sugars, 3,
Chapter 3 Glycosides and Disaccharides, 16,
Chapter 4 Oligosaccharides, 38,
Chapter 5 Ethers and Anhydro-sugars, 48,
Chapter 6 Acetals, 56,
Chapter 7 Esters, 61,
Chapter 8 Halogeno-sugars, 78,
Chapter 9 Amino-sugars, 85,
Chapter 10 Miscellaneous Nitrogen Derivatives, 101,
Chapter 11 Thio- and Seleno-sugars, 117,
Chapter 12 Deoxy-sugars, 121,
Chapter 13 Unsaturated Derivatives, 129,
Chapter 14 Branched-chain Sugars, 139,
Chapter 15 Aldosuloses and Dialdoses, 148,
Chapter 16 Sugar Acids and Lactones, 151,
Chapter 17 Inorganic Derivatives, 159,
Chapter 18 Alditols and Cyclitols, 165,
Chapter 19 Antibiotics, 177,
Chapter 20 Nucleosides, 194,
Chapter 21 N.M.R. Spectroscopy and Confonational Features, 217,
Chapter 22 Other Physical Methods, 228,
Chapter 23 Separatory and Analytical Methods, 238,
Chapter 24 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds, 253,

CHAPTER 1

Introduction and General Aspects

The past year has seen a continued development of the research area covered in this report towards specific biological applications of mono- and di-saccharides, especially the synthesis of disaccharides and oligosaccharides which are increasingly sought as probes for investigating immunological interactions, and the synthesis of analogues of antibiotics and nucleosides in the search for more effective antibiotics and antimetabolites. Nevertheless, the contents of the other chapters clearly indicate that wider aspects of monosaccharide chemistry continue to excite the interest of carbohydrate chemists, and also others who find carbohydrates convenient chiral sources for a wide range of biological compounds. Modern techniques of n.m.r. spectroscopy and mass spectrometry are also proving of great benefit for the analysis of complex carbohydrate structures. The fact that we record over 1400 references contributed by nearly 3000 workers speaks for itself!

Fringe areas have continued to pose a problem as to where to draw a line between carbohydrates and non-carbohydrate materials. In Chapter 4 we have concentrated on the synthesis of specific oligosaccharides, and the title of the report has been modified to reflect the distinction we wish to make between oligosaccharides occurring as such or attached to aglycones, which includes many antibiotics, and oligosaccharides recognized as structural units of polysaccharides. Likewise the coverage of other materials which are only part carbohydrate has been generally selective for those papers which discuss the chemistry of the carbohydrate moiety; obviously, distinctions are not always clear, and we hope that not too many papers get omitted which would be of interest to readers of this report.

Papers of more general carbohydrate interest published this year have included a description of a computer programme for selecting protecting groups of alcohols, ketones, and alkenes, details of a new ball-stick building set for sugars, and reviews (in Japanese) on the reaction of sugar derivatives with Grignard reagents (asymmetric reactions, acetal cleavage, deoxygenation of vic-diol monosulphonates, anomerization and ring-opening of furanosides) and on the application of electrochemical oxidation and reduction of carbohydrates. A relationship has been established for several carbohydrates between the partial molar heat capacity and the number of equatorial hydroxy groups in aqueous solution; exceptionally large values are caused by specific interaction of equatorial hydroxy groups with water molecules.

CHAPTER 2

Free Sugars

The processing of hardwoods to produce xylitol and other polyols monosaccharides and furfural is the subject of a Russian review. The methods for the preparation of lactulose from lactose have been reviewed.

1 Theoretical Aspects

A theoretical study of solvent effects on the free energies of cellobiose conformers, taking into account electrostatic, dispersion and cavity terms in ten solvents, has been carried out using the PCILO quantum chemical method: the main conclusion was that the structure observed in aqueous solution is similar to that found in the crystal. The solvent-induced conformational changes for β-cellobiose were compared with those for β-maltose and the differences attributed to the different solvation. Comparisons between calculated and observed n.m.r. spectra were made. initio calculations on water dimers with ten model geometries and seventeen which simulate the hydrogen bond contacts encountered in crystals of β-D-fructose, -arabinose, and -turanose examined the relationship between variations in geometry and hydrogen bond energy. The distance between the donor and recipient was varied and the calculated frequency shift was examined in relation to the hydrogen bond energy and the absorption intensity. The absence of a one-to-one relationship led to the conclusion that the observed variations are due to differences in the separation distances. The results were used to determine which hydroxy-oxygen contacts give rise to the narrow hydroxy i.r. bands observed in sugar crystals.

2 Synthesis

In a study of the formose reaction carried out in the presence of chitosan-lanthanum hydroxide, the sorption-desorption processes of the reaction and the stereochemical effectiveness were shown to depenu mainly on the pH of the medium.

Conversion of D-glucose to D-fructose proceeded in a maximum yield of 67.7% when catalyzed by disodium pentasilicate in aqueous methanol. The reaction was second order with an activation energy of 129 kJ mol-1 and proceeded faster with increasing concentration of methanol.

Hydrothermal equilibration of 1,3-dihydroxy-2-propanone and glyceraldehyde with their dehydration product methylglyoxal, a process related to the degradation of biomass, has been studied in the temperature range 180-240 °C.

A further paper on the use of deuterium displacement of the products of photobromination of anhydrosugars (see Vol.17, p.6) describes the synthesis of the two optical antipodes of D-[5-2H1] -ribose. The key reaction shown in Scheme 1 for the (5-R)-isomer proceeded with 100% optical purity in 80% chemical yield; the (5R)-and (5S)-isomers were obtained using the previously described procedures.

Chain-extension reactions via aldehyde additions have been used to synthesize higher aldoses, enuloses, branched-chain enuloses and 1-deoxy-alduloses. Addition of 2-lithio-1,3-dithiane to partially blocked carbohydrate derivatives proceeds in certain cases with high stereoselectivity; the authors suggest that the reaction is controlled by chelation of the oxygen functions at C — 1, C-2, and C-4 with the lithium cation as shown in formula (1) of Scheme 2. The same paper describes the reaction with 2,3;5,6-di-O-isopropylidene D-allofuranose to yield the heptose derivative (2) and its C-2 epimer in a ratio of greater than 30:1. Addition of 2-lithio-1,3-dithiane to 2,3:5,6-di-O-isopropylidene-D-mannofuranose gave rise to the D-glycero-D-galacto-isomer (3) which was converted via a sequence involving oxidation at C-7 and reduction at C-1 into L -glycero-D-mannoheptose (4) Stereocontrolled homologation of α-hydroxy aldehydes has also been achieved by addition of silazoles. Thus the protected derivative (5) of D-erythrose was preparable from 2,3-O-isopropylidene-D-glyceraldehyde as shown in Scheme 3; using the same sequence on (5)> the D-ribose derivative (6) was prepared. The Wittig reaction using the reagents (7) and (8) on 2,3-iso -propylidene-D-glyceraldehyde also proceeded stereoselectively; in the case of (7), the (E)-isomer (9) predominated over the (Z)-isomer (10) by 64% to 25% isolated yield, while (8) gave exclusively the (E) -product (11). Hydroxylation of (9) with osmium tetroxide-potassium chlorate was used to synthesize 1-deoxy-D-tagatose and 1-deoxy-D-psicose as shown in Scheme 4.

Catalytic osmylation of the allylic ethers and alcohols (12) led to the octose derivative (13) as the predominant isomer; the (Z)-alkene (14) gave the 7-epimer (15), in agreement with the empirical rule of Kishi that there will be an erythro-relationship between the oxygens at C-5 and C-6. The reaction sequence was also extended to the synthesis of decose derivatives. The hydroxylation of the α,β-unsaturated ester derivative (16) yielded the erythro-acetal (17). Reduction of the diacetate of (17) with lithium aluminium hydride followed by acid hydrolysis and deacetylation gave DL-erythrose. A similar sequence starting with the (E)-isomer of (16) led to DL-threose. (+)-Di-isopropyl tartrate catalysed t-butylperoxide epoxidation of the unsaturated acetal (18), itself prepared by Grignard addition to aldehyde (19), gave a mixture of the ribo- and lyxoisomers (20) and (21) in a ratio of 24.: 1- Separation and base-catalyzed ring opening of (20) yielded the ribo-hexose (22), acid hydrolysis of which gave 2.6-dideoxv-DL-ribo-hexose (23) (Scheme 5). The total synthesis of methyl 3,4,5-tri-O-acetyl-1,7-di-O -benzyl-α-DL-gluco-hept-2-ulopyranoside (24) has been achieved (Scheme 6).

The product of the reaction between the isomaltol α-D-glycosides (25) with triethylamine-pyrroliaine has been shown to be the corresponding 1 ,6-anhydro-β-D-glycopyranose, formed by the internal displacement of isomaltol as shown in Scheme 7. The isomaltol (26) gives a polymer, which is also produced in the browning reaction.

1-O-Acetyl groups in substituted hexopyranoses may be hydrolyzed by aqueous tin(IV) chloride. The reaction is complete within 1h; trans-1,2-acetoxy groups.are hydrolyzed at RT, whereas a temperature of 40 °C is required for 1,2-cis compounds. The method is satisfactory in the presence of 2-phthalimido and 2-O-tosyl groups, while for perbenzyl 1-acetates it is virtually quantitative. 1,2-Trans-di-acetoxy compounds do not give complete formation of the glycose due to a migration of the 2-O-acetyl group to C-1. Regioselective 1-O-deacylation of peracylated glycopyranoses has also been achieved using ammonia in an aprotic solvent such as acetonitrile, dimethoxy-ethane, or THF, sometimes with the addition of a little methanol. The reaction proceeded in high fiield at room temperature. Two examples are shown in Scheme 8.

Galactose oxidase has been used to prepare L-sugars from alditols; the conversions are incomplete due to product inhibition of the enzymes. The general arrangement shown in (27) is necessary although not all examples are good substrates; it was found that addition of ferricyanide ion increased the reaction rate. The enzyme was used to prepare L-xylose, L-galactose, L-glucose, and D-threose, following Scheme 9.

3 Physical Measurements

The n.m.r. line width and saturation transfer method has been used to determine the thermodynamic and kinetic parameters for ring-opening and closing of aldo- and ketofuranoses and their phosphate esters. The kinetics of the mutarotation of sugars have been determined using an h.p.l.c. technique, in which the change in the chromatogram with time following dissolution of a pure anomer in water was determined. For the α-L-rhamnopyranose-β-L-rhamnopyranose equilibrium the rate constant was determined to be 6.8 x 10-4 s-1 at 25° in good agreement with values from optical rotation methods. The equilibrium of anomers in different solvents was also studied.

Excess enthalpies of aqueous solutions of aldopyranosides have been measured at 25° and the self- and cross-interaction coefficients determined. The same microcalorimetric methods were used to measure the excess enthalpies of eight ternary aqueous solutions of four aldopentoses and either glycine or N-acetylglycinamide at 25 °C. The results showed that these amino-acids do not provide good models for the peptide-sugar interactions (see also Vol.18, p.7). A rigorous method of analysis has been applied to determine the temperature dependent activation parameters for sucrose hydrolysis. It was concluded that the inclusion of a temperature dependent activation enthalpy was unwarranted.

Sugar-water interactions have been evaluated from diffusion measurements. The Stokes-Einstein relation for mono- and trisaccharides was discussed and the diffusion coefficients for D-ribose and 2-deoxy-D-ribose were measured. The latter has the larger co-efficient , showing that 2-deoxy-ribose breaks the local water structure, whereas D-ribose hardly affects the structure. It was suggested that the mean number of equatorial hydroxy groups is a good parameter for describing sugar hydration properties. It has been demonstrated that, over a wide range of concentration, the ideal and non-ideal solution models of D-glucose are inadequate unless hydration is taken into account. A hydration number of 3.5 was found for molecular D-glucose, while dissociated D-glucose ions are not hydrated: this result was discussed in relation to intramolecular hydrogen bonding within D-glucose ions produced in alkaline isomerization reactions. A study by 13C n.m.r. spectroscopy of D-idose using partially deuterated hydroxy groups has shown that intramolecular hydrogen bonding stabilizes the α-pyranose in the 4C1 conformation in non-aqueous solvents (see also Chapter 21). The constants for H-bridging complex formation between D-glucose, cellobiose, xylose, and phenol as models for cellulose and different 0-basic dipolar molecules such as N-methyl-caprolactam, HMPA, and DMSO in chloroform and ethanol have been determined. Evidence of hydrogen bonding in D-fructose as shown in (28) has been obtained from variable temperature high field n.m.r. spectroscopy. The preponderance of the β-furanose form in DMSO is attributed to this feature. The kinetics of the tautomeric equilibria were studied.

The concentration and structure of free radicals generated in D-glucose, lactose and cellulose by [[??]-irradiation have been determined by the chemiluminescence produced on contact with distilled water or aqueous solutions of various substances. It was possible to distinguish between singlet oxygen and excited carbonyl species by the wavelength of the chemiluminescence (630 nm and 500 nm respectively). [??]-Irradiation of cellobiose gave a paramagnetic intermediate formed by cleavage of the C-5-0 bond as shown by e.s.r. spectroscopy. A mechanism for radiolysis of cellobiose was proposed. E.s.r. spectroscopy has also been used to show that the source of lyoluminescence in irradiated L-rhamnose is the recombination of generated peroxide radicals to yield carbonyl-containing species.

The density, viscosity, and ultrasonic velocity of aqueous D-fructose solutions in the presence of metal ions have been determined at 30 °C. Partial molal volumes, partial molal compressibility, free energy change, and viscosity B-coefficients of these solutions were calculated from the data. It was concluded that solvent-solute interactions are suppressed in the presence of metal ions. “Hydrophobic indices” calculated from the hydrophobic and hydrophilic surface areas of seven monosaccharides were calculated and found to correlate with the partition coefficients between polystyrene gel and water and with the free energy change for transfer from water to butanol. The hydrophobic surface area was defined as the surface area occupied by methine and methylene groups and the hydrophilic surface as that occupied by hydroxy and ether oxygen functions. Different conformations of anomers of pyranose and furanose forms were considered where appropriate.

When manganese(III) ions are used to induce reaction between hypobromous acid and sugars, oscillations appear in the potential of a platinum electrode in the solution. Nine common mono- and disacccharides were studied by such polarography and sustained oscillations of the Belousov-Zhabotinsky type were noted when a nitrogen flow was used. N.m.r. spectroscopy of D-[2-13C] fructose has been used to study its mutarotation in alkaline solution. Thermodynamic parameters for the interconversion of the α and β-furanose forms, the β-pyranose and the keto-form were determined.

4 Oxidation

A mechanism for the oxidation of D-ribose with cerium(IV) in sulphuric acid has been proposed on the basis of its kinetics, Activation parameters for the oxidation of D-glucose, D-galactose, D-mannose and D-gulose by silver(I) and mercury(II) ions at pH 1 have been determined. Rate constants were linearly related to the free energy of aldose equilibrium forms as well as to the redox potentials of the oxidants. The kinetics and mechanisms of oxidation of D-glucopyranose 6-phosphate and D-ribofuranose 5-phosphate by chromium (VI) in perchloric acid media have been determined using u.v. spectroscopy. The reactions were acid catalyzed and accelerated by the addition of sodium perchlorate. There is a variable dependence of rate on the concentration of oxidant and hydrogen ion concentration in the oxidation of D-fructose by vanadium(V) ions. The kinetic data and activation parameters were compared with those for simpler mono- and polyhydric alcohols, and a three-step mechanism involving C-H fission yielding glucosones as primary products has been suggested. The oxidation of diols as models for starch and cellulose using manganese(III), cerium(IV), and vanadium(V) ions has been studied using u.v. and e.s.r. spectroscopy. The reaction was thought to proceed via a stable complex and showed a first order dependence on hydrogen ion concentration. Acyl radical spin adducts were detected as intermediates from aldehydes and diols by spin trapping techniques. Cis-1,2-diols were oxidized four times as fast as cis-3.4-diols, while trans-diols and isolated primary hydroxy groups showed negligible reactivity. It was concluded that C-1 – C-2 and C-2 – C-3 diols are the predominant sites on the polysaccharides for the initiation of graft co-polymers. In the oxidation of melibiose and cellobiose by tetramminecopper(II) in ammoniacal and buffered media the rate of reaction is first order in disaccharide concentration, order one half in ammonia concentration, and independent of the concentration of copper(II). On addition of ammonium chloride, the rate is decreased by the common ion effect. A mechanism involving an intermediate enediolate ion with the rate of reaction being equal to the rate of enolization was proposed. The kinetics and mechanism of thallium(III) oxidation of cellobiose in acid medium have been determined: the acid-catalyzed reaction was first order in each reactant, and the active oxidant was thallium(III) diacetate. The sugar products were identified as D-gluconic acid and glucose.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 19 by N. R. Williams. Copyright © 1987 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.