Carbohydrate Chemistry Volume 20 Part 1

Monosaccharides, Disaccharides, and Specific Oligosaccharides

By N. R. Williams

The Royal Society of Chemistry

Copyright © 1988 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-242-2

Contents

Chapter 1 Introduction and General Aspects, 1,
Chapter 2 Free Sugars, 2,
Chapter 3 Glycosides and Disaccharides, 18,
Chapter 4 Oligosaccharides, 43,
Chapter 5 Ethers and Anhydro-sugars, 53,
Chapter 6 Acetals, 62,
Chapter 7 Esters, 68,
Chapter 8 Halogeno-sugars, 84,
Chapter 9 Amino-sugars, 92,
Chapter 10 Miscellaneous Nitrogen Derivatives, 106,
Chapter 11 Thio-sugars, 118,
Chapter 12 Deoxy-sugars, 122,
Chapter 13 Unsaturated Derivatives, 130,
Chapter 14 Branched-chain Sugars, 141,
Chapter 15 Aldosuloses, Dialdoses, and Diuloses, 151,
Chapter 16 Sugar Acids and Lactones, 155,
Chapter 17 Inorganic Derivatives, 167,
Chapter 18 Alditols and Cyclitols, 174,
Chapter 19 Antibiotics, 186,
Chapter 20 Nucleosides, 201,
Chapter 21 N.M.R. Spectroscopy and Conformational Features, 226,
Chapter 22 Other Physical Methods, 236,
Chapter 23 Separatory and Analytical Methods, 247,
Chapter 24 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds, 258,
Author Index, 275,

CHAPTER 1

Introduction and General Aspects

The following chapters represent a survey of monosaccharide and selected oligosaccharide research reported in 1986. Whilst we have attempted to be comprehensive in our coverage of monosaccharide chemistry, certain topics embracing both carbohydrate and non-carbohydrate components have been selective for those papers reporting specific carbohydrate chemistry, and in some other areas it has been difficult to decide whether extensively modified derivatives can be regarded as being carbohydrate at all, and we have used our own judgement in deciding whether or not to include such papers. The trends in research interest established in our recent reports have been maintained, and, in particular, efficient methods for synthesizing glycosides have been widely applied to an increasing range of compounds of ever-increasing complexity. Natural products still have many surprises in store, as evidenced by the discovery of the antibiotic oxetanocin, a nucleoside analogue possessing a four-membered sugar ring; other antibiotics apparently contain novel thio-sugar components. We have reviewed about 1460 references for this report.

Reports on more general aspects of carbohydrates have included reviews on “the sweeter side of chemistry”, synthetic control in the synthesis of carbohydrates, the use of the hetero Diels-Alder reaction in synthesizing 1,4-difunctionalized pentoses and hexoses from furans, the application of phase-transfer catalysis to carbohydrate chemistry, and the use of stable isotopes in carbohydrate chemistry.

CHAPTER 2

Free Sugars

1 General and theoretical aspects

The reactions of monosaccharides in aqueous alkaline solution is the subject of a review covering initial transformations, alkaline degradation and the influence of reaction variables on product formation.

Molecular orbital calculations have been carried out in an investigation of the mechanism of mutarotation of α-D-glucopyranose. The CNDO/2 results were in agreement with experiment for acid- and base-catalyzed processes. A molecular dynamics simulation of the 1C4 and 4C1 conformations of α-D-glucopyranose in vacuo predicts very flexible rings. The mean dynamic structure was found to be close to the structure found in the crystal, but there was a deviation in the C-5 – O-5 region.

A far-reaching communication has concluded that there is an intrinsic energy difference between enantiomeric chemical species. The results, from an ab initio calculation, depend on “parity-violating weak interactions” due primarily to the electron-neutron potential component of the weak neutral current present in atomic nuclei. Application to the model sugar, hydrated glyceraldehyde, indicated that the D-enantiomer is of lower energy, which, if taken as a free energy difference, corresponds to an enantiomeric excess of ~106 molecules per mole. The suggestion is that this difference is the cause of the preference for D-sugars in nature.

2 Synthesis

A review on asymmetric epoxidation of allylic alcohols by the Sharpless method includes discussion of its use for the de novo synthesis of sugars and polyols and for further extension of sugar-derived allylic alcohols for chiral synthesis from sugars.

The one-step synthesis of straight chain carbohydrates from formaldehyde and syngas (hydrogen and carbon monoxide in a 2:1 ratio) has been described. The process involves heating paraformaldehyde in pyridine and tertiary amine in the presence of bistriphenylphosphine -carbonyl rhodium chloride under an atmosphere of syngas in an autoclave. The product contained up to 60% total carbohydrate which consisted of straight chain sugars with between two and six carbon atoms. The results are thus different from those obtained in the formose reaction which gives a large proportion of branched-chain products. The formose reaction in the presence of fructose and the alkaline degradation of fructose in the presence of formaldehyde have been investigated and compared. The study was prompted by the observation that formaldehyde added for microbiological control in the sugar industry is decomposed in the presence of invert syrup during the liming process. It was concluded that aldolization and retroaldolization reactions are of major importance and that there is no essential mechanistic difference between the two reactions. Pentoses and hexoses are formed in 48 hours from glyceraldehyde on sodium montmorillonite clay at 40° in aqueous dispersion. The sugars were formed in the interlamellar regions of the clay and the resultant intercalates were found to be stable to 250 °C.

A convenient preparation of L-(S)-glyceraldehyde acetonide from L-ascorbic acid en route to glycerol acetonide is described more fully in Chapter 24. An alternative method to that of Dondoni et al. (see Vol. 19, p.4) for the homologation of D-glyceraldehyde to prepare derivatives of D-erythrose (1) and D-threose (2) has been described; with appropriate reagents, either the erythro-epimer (3) or the threo-epimer (4) could be obtained as the major product (Scheme 1). Application of a further reaction sequence to the acetonide (1) yielded allitol hexa-acetate (5).

Two convenient methods for the synthesis of L-erythrose from D-ribono-1,4-lactone have come from the same laboratory. In the first, the 2,3-O-isopropylidene derivative is subjected to sequential reduction to the ribitol, periodate oxidation, and deprotection, second route similarly utilized 3,5-O-benzylidene-D-ribono-1,4 -lactone.

L[-4-2H]Erythrose (6), L-[1-13C, 5-2H]arabinose (7), L-[113C, 5-2H]ribose (8) and L-[2-13C, 5-2H]arabinose (9) have been synthesized from L-rhamnose as shown in Scheme 2. Condensations using 2-substituted 1,3,2-dioxaboroles provide a means for extending the chain length of a sugar by two carbon atoms. The reagent was most conveniently used by attachment to a polymer. The application of the method to 2,3-O-cyclohexylidene-L-glyceraldehyde is shown in Scheme 3.

L-Glucose has been synthesized by the route shown in Scheme 4.

The Diels-Alder reaction of the substituted butadiene and benzaldehyde proceeded under asymmetric induction due to the substituted menthyl moiety.

Conversion of alditols to aldoses without the need to protect all hydroxy groups has been achieved by monotosylation of one primary hydroxy group, displacement with azide ion and photolysis in methanol to yield the aldimine, which was then hydrolyzed to the aldose. The procedure was illustrated using 3,4-O-isopropylideno-D-mannitol to produce D-mannose. The synthesis of D-[U-14C]galactose from methyl α-D-[U-14C]glucopyranoside via aqueous bromine oxidation to the 4-uloside, reduction by sodium borohydride and hydrolysis has been described, along with the isolation of D-glucuronic acid and methyl α-D-mannopyranoside as by-products.

The Knoevenagel-Doebner reactions of 2,3-O-isopropylidene-D-ribofuranose and 2,3:5,6-di-O-isopropylidene-D-mannofuranose have been studied (Scheme 5). The products were found to be epimerized at the original C-2 position.

2,3-O-Isopropylidene-β-D-tagatopyranose (10) has been synthesized from 1-O-benzoyl-2,3:4> 5-O-isopropylidene-β-D-fructopyranose (11). The required inversion at C-4 was effected by oxidation – reduction of the 4-hydroxy derivative (12), but the reduction showed poor stereoselectivity and gave the C-4 epimers (12) and (13) in a 1:1 ratio. The regioselective 5-O-benzylation to generate (12) was achieved via a 4,5-O-dibutylstannylidene derivative (Scheme 6).

Synthesis of the higher sugars is currently attracting much interest and papers covering the range up to decoses have appeared. Reaction of D-mannose with nitromethane in the presence of sodium methoxide followed by treatment with sulphuric acid gave D-glycero -D-galacto-heptose. Sequential hydrogenation of the octynopyranose (14.) using Lindlar catalyst and hydrogen, ozonolytic cleavage of the alkenyl products, and reduction of the ozonide gave methyl 2,3,4 -tri-O-benzyl-α-D- and -L-glycero-D-gluco-heptopyranosides. Cyanide addition to the manno-dialdose (15) has been used in the synthesis of D- and L-glycero-D-manno-heptose. The addition was accompanied by epimerization at C-5, presumably by β-elimination and addition (Scheme 7). L-glycero-D-manno-Heptose, a constituent of the inner region of lipopolysaccharides, has also been synthesized by chain-extension of 2,3:5,6-di-O-isopropylidene-α-D-mannofuranose using dithiane, the corresponding alditol being inverted to the required heptose by standard reactions.

A review on the occurrence and preparation of D-mannoheptulose has appeared. Full papers have been published by Brimacombe’s group on their syntheses of octoses and decoses by D-chain extension of dialdose derivatives to alkenyl derivatives which were then subjected to stereospecific hydroxylation procedures. (See Vol. 19, p.6, refs. 14,15. Inadvertently the report indicated D-threo and L-erythro products as the major products; the correct data are shown in Scheme 8.)

Conventional degradations of the appropriate octoses were also used to prepare L- and D-glycero-D-manno-heptose. The preparation and identification of aldolization products formed by treatment of 1,3-dimethoxy-2-propanone with aqueous sodium hydroxide at 5 °C has been reported. The products included the branched-chain pentose, heptose, and nonose derivatives (16) – (18).

The synthesis of sugars by iterative, diastereoselective homologation of aldehydo-sugars with 2-trimethylsilylthiazole mentioned last year (see Vol. 19, p.5, ref. 11) has been extended up to nonose derivatives. The newly created chiral centre at C-2 invariably bore an erythro relationship to the C-3 substituent; thus, D-glyceraldehyde led to the D-allose derivative (19), and the mesooctitol (20) was obtained via the corresponding octose.

A Wittig reaction on aldehydo-2,4,5,6-tetra-O-methyl-D-glucose gave the Z-oct-2-enonic acid derivative (21), which yielded the lactone (22), an intermediate for synthesizing octoses. Wittig reagents prepared from sugars have also been used to synthesize potential intermediates for higher sugars; Scheme 9 illustrates such a synthesis, coupling two sugar units tail-to-tail, to give a dodecose derivative.

Enzymic coupling of sugar phosphates by aldolase has been used to prepare octoses and nonoses (Scheme 10). The method was shown to be suitable for coupling deoxy and amino-deoxy sugars. The dianion of the glucofuranosyl sulphone (23) has been reacted with carbon electrophiles to yield higher sugar sulphones (24.). The same paper also reports chain extension of dialdehydo nucleosides such as (25) by means of Wittig reactions.

Allosucrose, α-D-allopyranosyl-β-D-fructofuranoside, has been prepared from sucrose using an oxidation-reduction sequence to invert the C-3-hydroxy group.

3 Physical measurements

The direct measurement of the rate of ring-opening of D-glucose by aldose reductase-catalyzed reduction has been reported. The results for this direct measurement of D-glucose and 5-thio-D-glucose support the prediction that base-catalyzed mutarotation proceeds primarily through the acyclic carbonyl intermediate for simple sugars. The effect of cations on the anomeric equilibrium of D-glucose in aqueous solutions has been studied by Raman spectroscopy in the 950 – 800cm-1 region. The calcium ion has a marked effect in shifting the equilibrium towards the α-anomer. The magnitude of this effect was found to decrease in the sequence Ca2+ >Sr2+ ≈ La3+ > Na+ ≈ Zn2+ > Cd2+ [approximately equal to] Mg2+ ≈ K+ as determined by the proportion of the α-anomer present. D -Idose in deuterium oxide exists as 13.5% α-furanose, 16.5% β-furanose, 35.9% α-pyranose, 33.4% β-pyranose, 0.5% aldehydrol and 0.1% aldehydo forms as measured with 13C n.m.r. of 13C-enriched compounds. For D-glycero-D-ido-heptose the corresponding proportions were 8.7, 15.5, 24.4, 50.8, 0.6, and 0.06%. The technique allowed the unidirectional rate constants for ring-opening and closing of the furanoses and pyranoses to be determined. Isomer distribution of D-fructose in water, DMSO and pyridine has been determined by examination of 1H n.m.r. intensities of the C-2 hydroxy protons. Experiments were carried out in [d6]DMS0, or in other solvents by freezing the samples with liquid nitrogen and dissolving in DMSO with rapid determination of the n.m.r. spectrum. At 25° the β-furanose predominated in DMSO whereas in water and pyridine the most abundant form was the β-pyranose. The rate constants for all the reactions in the interconversion of the pyranose, furanose, and aldehydo forms of 2-deoxy -D-erythro-pentose have been determined by n.m.r. methods. Kinetic and thermodynamic parameters for the thermal and photochemical mutarotation of α-D-glucose in DMSO have been measured and a mechanism proposed.

An investigation of the relationship between sweetness and structure of chlorinated sugars has been carried out using Fourier transform i.r. to examine the states of the hydroxy groups. It was concluded that the sweet compounds contained hydroxy groups which were not involved in hydrogen bonding and that chloro functions enhance sweetness by increasing lipophilicity.

Enthalpies of solution of α-D-glucose, β-D-glucose, α-D-galactose, and α-D-mannose in water-DMF mixtures at 298.15K have been reported for the whole mol fraction region. Exothermic deviations from linear behaviour result from preferential hydrogen-bonding of functional groups and hydrophobic hydration of the apolar surfaces of the solute. Differences in solvation enthalpy of the four hexoses were related to differences in their conformations. Results of calorimetric measurements of mean molar heat capacities of sugars have been reported. Derivatives of D-galactopyranose, DL-2,3,4-trideoxy -glycero-hex-2-enopyranose, and DL-ribopyranose were studied, and the heat capacity contributions of the pyranose rings in these sugars confirmed the existence of different energy levels found previously from semi-empirical calculations for the different conformations of the pyranose ring. Conformation entropies for a series of mono- and higher saccharides including O-methyl derivatives have been predicted from rotational prohibition rules and found to agree satisfactorily with known entropies of D-aldohexopyranoses. The heats of dilution of aqueous solutions of cellobiose, maltose, trehalose, and melizitose have been determined by flow microcalorimetry, and the influence of urea in these solutions was studied. In some cases ‘excess’ thermodynamic properties could be determined. Pyrolysis of glucose, maltose, cellobiose, amylose, and cellulose has been studied by thermogravimetry between 250 – 400° under helium at atmospheric pressure. The mechanism of cryoprotection in living cells and liposome dispersions by mono-, di-, and tri-saccharides has been investigated by differential scanning calorimetry and Raman spectroscopy of aqueous sugar solutions at low temperatures, methods which determine the amount of ‘unfreezable water’ bound to the sugars.

A kinetic study of the acetone-sorbose reaction on an ion-exchange resin, KU-23, showed that the reaction could be interpreted in terms of two types of water in the catalyst; one of these blocks the active sites while the other is involved in diluting the reactants. A dielectric study of sorbed water on galactose has been carried out using a depolarization thermocurrent method on compressed pellets of hydrated galactose. The modes of binding of water molecules in the temperature range 80 – 300K and water contents between 2.2 and 20.8% were investigated; measurements revealed two dielectric dispersion regions, one attributed to reorientation of sorbed water. Three discrete relaxation mechanisms contribute to second dispersion at higher temperatures. The hydrophobic properties of sugars and their implications in nutrition and food science have been reviewed.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 20 Part 1 by N. R. Williams. Copyright © 1988 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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