Carbohydrate Chemistry Volume 29

Monosaccharides, Disaccharides and Specific Oligosaccharides

By R.J. Ferrier

The Royal Society of Chemistry

Copyright © 1997 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85404-213-5

Contents

Chapter 1 Introduction and General Aspects, 1,
Chapter 2 Free Sugars, 3,
Chapter 3 Glycosides and Disaccharides, 16,
Chapter 4 Oligosaccharides, 63,
Chapter 5 Ethers and Anhydro-sugars, 91,
Chapter 6 Acetals, 98,
Chapter 7 Esters, 103,
Chapter 8 Halogeno-sugars, 118,
Chapter 9 Amino-sugars, 122,
Chapter 10 Miscellaaeous Nitrogen Derivatives, 146,
Chapter 11 Thio- and Seleno-sugars, 170,
Chapter 12 Deoxy-sugars, 176,
Chapter 13 Unsaturated Derivatives, 182,
Chapter 14 Branched-chain Sugars, 191,
Chapter 15 Aldosuloses and Other Dicarbonyl Compounds, 205,
Chapter 16 Sugar Acids and Lactones, 208,
Chapter 17 Inorganic Derivatives, 219,
Chapter 18 Alditols and Cyclitols, 225,
Chapter 19 Antibiotics, 252,
Chapter 20 Nucleosides, 268,
Chapter 22 Other Physical Methods, 324,
Chapter 23 Separatory and Analytical Methods, 346,
Chapter 24 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds, 357,

CHAPTER 1

Introduction and General Aspects

An appreciation has been written of the seminal, major contributions of H.S. Isbell to carbohydrate chemistry.

Several carbohydrate applications have been included in a review of microwave-assisted organic reactions, and a survey of chemical reagents in photo-affinity labelling included the role of various base-labelled azido- and thio-nucleosides, sugar azide derivatives and p-benzoylbenzoate esters of nucleosides. A further review intitled ‘Reverse Anomeric Effect: Fact or Fiction?’ refers to early evidence based on studies of glycosyl pyridinium and imidazolium salts. It concludes that its origin as an electronic effect is not supported by theory or experimental results.

A review in ‘Advances in Carbohydrate Chemistry and Biochemistry’ has covered 13C-1H coupling in sugar derivatives and included theoretical aspects, experimental techniques and conformational dependencies. A related survey was produced on 13C nuclear magnetic relaxation and motional behaviour of carbohydrates in solution. Theoretical and observed data were included.

Part I of a review on the uses of enzymes in carbohydrate chemistry has appeared, this part dealing with biological recognition and syntheses of monosaccharides and analogues including amino-sugars. A further essay on applications of enzymes deals with the use of glucansucrase in the synthesis of oligosaccharides and polysaccharides. The chemotherapy of HIV infection has been surveyed with attention being given to the various applications used and targets identified. Nucleoside analogues and glucosidase inhibitors were discussed amongst the drugs used.

An in-depth treatment of the organic chemistry of the monosaccharides also briefly covers their role in natural products, for example glycosides, oligosaccharides, polysaccharides and glycoproteins. Such topics as the chemical synthesis of oligosaccharides and the use of sugars in the synthesis of enantiomerically pure non-sugar products are dealt with after an extensive mechanistic treatment of the reactions of the monosaccharides. Containing 1000 references, the book provides a convenient means of access to the primary literature.

CHAPTER 2

Free Sugars

1 Theoretical Aspects

A sytematic search has been made for all low energy structures of α- and β-D-glucopyranose, α- and β-D-galactopyranose, β-D-talopyranose and β-D-allopyranose in the solid state, the energies being minimized with respect to nine lattice and rigid-body parameters and six intramolecular dihedral angles. In four cases, the observed crystal structures corresponded to one of the lowest energy structures; in the other two cases, the observed structures were of more than 20 kJ mol-1 higher energy than the calculated minima. An extension of the GROMOS force field allowed an improved crystal structure determination of α-D-galactopyranose.

The hydroxyl acidities of sucrose, assessed through semiempirical calculations of the deprotonation enthalpies, followed the order OH-2g [much greater than] OH-3g > OH-3f > OH-1f = OH-4g > OH-4f [much greater than] OH-6g > OH-6f. The molecular electrostatic potential profile of sucrose in polar, aprotic solvents indicated likewise that in the main conformation OH-2g is the most electropositive hydroxyl group; the preparations of selectively benzylated and acetylated sucrose derivatives on the basis of these findings are referred to in Chapters 5 and 7, respectively.

The hydration of α-maltose has been investigated using molecular modelling and thermodynamic methods. Due to crystallinity, the observed non-freezing water content was lower than that calculated.

Conformational studies on several free sugars are covered in Chapter 21.

2 Synthesis

A review article on enzymatic oxidoreduction in organic synthesis included the following carbohydrate-related topics: i) oxidation of polyols to polyhydroxy aldehydes by use of galactose oxidase (yields 10-15%); ii) the reduction of 2-acetylfuran by alcohol dehydrogenases from two different sources to furnish enantiospecifically either the (R)-alcohol 1 or its (S)-isomer 2, which serve as potential building blocks for the synthesis of D- and L-sugars, respectively.

Aldolase- and transketolase-catalysed synthesis of pentoses, hexoses and higher sugars continues to receive considerable attention, especially by C.-H. Wong and co-workers who have covered these processes in Part 1 of a review article (60 refs.) on the use of enzymes in carbohydrate chemistry. DERA (deoxyribose 5-phosphate aldolase, EC 4.1.2.4) has been prepared on a large scale by recombinant techniques. It was employed, either by itself or in combination with RAMA (rabbit muscle aldolase, a fructose-1,6-diphosphate aldolase, EC 4.1.2.13) or NeuAc aldolase (EC 4.1.3.3 ) and, if necessary, phosphatase in sequential condensations to afford deoxyaldoses from -pentoses to -nonoses from small substrates such as acetaldehyde, glyceraldehyde and dihydroxyacetone phosphate. Condensations catalysed by L-fuculose 1-phosphate aldolase (EC 4.1.2.17) and L-rhamnulose 1-phosphate aldolase (EC 4.1.2.19), in combination with phosphatase and the appropriate isomerases, resulted in efficient syntheses of L-fucose and L-glucose, respectively. An alternative strategy to prepare aldoses by this process which initially produces doses, is illustrated in Scheme 1. Similar condensations involving the masked hydroxydialdehydes 3 and 4 were used in the synthesis of aldoketose derivatives 5 and 6, respectively, required as precursors for the microbial preparation of deoxynojirimycin analogues. The condensation of pyruvate with simple hydroxyaldehydes, e.g., D-glyceraldehyde or D-erythrose, under catalysis by an aldolase from Aspergillus terra gave 3-deoxy-2-ulosonic acids with (R)-configuration at the new chiral centre (C-4).

2.1 Tetroses and Pentoses. – The application of the Strecker synthesis to the preparation of 2-amino-2-deoxytetrose derivatives is covered in Chapter 9 and a lipase-mediated route to 4-carbon diols and triols is referred to in Chapter 18. The CaCl2/KOH-promoted aldol condensation of dihydroxyacetone with formaldehyde has been optimized for the production of D,L-threo-3-pentulose. L-Ribofuranose derivatives have been obtained in good yields from 1,2-O-isopropylidene-5-O-trityl-α-L-xylofuranose by oxidation-reduction at C-3. The efficient preparation of the D-ribose derivative 8 from the corresponding lactone 7 was one of twelve examples in a paper describing the catalytic reduction of 1,4- and 1,5-lactones to the corresponding lactols by use of the reagents indicated in Scheme 2. A new synthesis of 1-deoxy-D-threo-pentulose in eight steps from (-)-tartaric acid is referred to in Chapter 12 and the preparation of D-lyxose and D-arabinose in high yields by oxidative degradation of D-galactose and sodium D-gluconate, respectively, is covered in Section 5 of this Chapter.

2.2 Hexoses. – Isopropylidene-D-glyceraldehyde (9) has been converted to a six-carbon sugar precursor with introduction of one new chiral centre in a lengthy reaction sequence involving Wittig-Homer elongation by two carbons and Sharpless asymmetric epoxidation, followed by one-carbon extension via diazoketone 10, which gave 11 on photolysis (Scheme 3).

Efficient procedures for the conversion of levoglucosenone to rare sugars, e.g., D-altrose, D-allose, 4-deoxy-D-mannose, have been devised. Hydrolytic opening of the L-sorbopyranose-derived epoxide 12 with nucleophilic attack at C-4 was the key-step in the transformation of L-sorbose to L-fructose, which requires inversion of configuration at C-3 and C-4. The formation of D-tagatose from D-galactose involving oxidation at C-2 and reduction at C-1 was facilitated by the spontaneous cyclization of the osulose intermediate 13 to the bicyclic hemiketal 14. This was readily O-methylated to 15, thus offering convenient protection for the carbonyl group during the subsequent reduction step.

D-Tagatose 3-epimerase (see Vol. 28, Chapter 2, Ref. 64) immobilized on Chitopearl beads, was employed for converting D-tagatose to D-sorbose on a multigram scale. By use of the same enzyme preparation, D-psicose was available from D-fructose or, in the simultaneous presence of D-xylose isomerase, from D-glucose. The preparation of L-tagatose from 1,5-anhydro-D-galactitol via ‘L-2-sorbal’ is mentioned in Chapter 13 and a synthesis of L-fucose from D-galactose is covered in Chapter 12.

2.3 Chain-extended Sugars. – A review on two-directional synthesis involving desymmetrization of chain-extension products contained several examples of higher alditols, aldoses and aldonic acids. A section on the synthesis of higher carbon sugars has been included in a review dealing with the application of furan-and pyrrole-based siloxydienes. The cycloaddition product formed from penta-2,4-dienol (16) and sodium glyoxalate (17) at 100°C in aqueous medium was converted to the racemic methyl 2,3-dideoxyheptulosonate triacetates 18, as shown in Scheme 4. These were further processed to furnish 3-deoxy-2-heptulosonic acid derivatives 19. By use of tetrose-based dienes 20, this approach has also been adapted to the synthesis of 3-deoxy-2-nonulosonic acid derivatives. Many chain-extended monosaccharides have been prepared by enzymatic aldol condensations (see Refs. 7-14 above).

2.3.1 Chain-extension at the ‘Non-reducing’ End. – As usual, protected dialdoses have been used extensively for this purpose. Stereoselective hydroxymethylation of 21 to give the methyl L-glycero-D-manno-heptopyranoside derivative 23 was achieved by treatment with [dimethyl(thiophenylmethyl)silyl]methylmagnesium chloride followed by oxidative desilylation of the addition product 22. The addition of methyl nitroacetate to 24 furnished an inseparable mixture 25 in mediocre yield; reduction of the nitro groups was inefficient but the resulting amines 26 could be separated. The indium-mediated allylation of 27 (see Vol 28, Chapter 2, Ref. 47) showed high anti-diastereofacial selectivity in the presence of Lewis acids, especially Y(OTf)3, thus affording mainly the 4,5-erythro product 28.

erythro-Addition was also favoured in the condensations of sugar-derived aldehydes with acetyliron anions (see Vol. 28, Chapter 2, Ref. 28) when counterions other than Li (e.g., Sn2+, Zr4+, Et2Al+) were used; as an example, the preparation of 6-deoxy-β-D-allo-heptopyranose pentaacetate (30) from 29 is given in Scheme 5.

Addition of alkylmanganese reagents, prepared in situ from the corresponding alkyl lithium compounds and MnI2 in ether, to substrates 24 and 27 proceeded diastereoselectively to give 4,5- and 5,6-threo products, respectively. Spiroketals 31 have been synthesized from methyl 2,3,4-tri-O-methyl-α-D-glucopyranoside by a radical method similar to that shown in Scheme 7 below. Reformatzki reaction of 32 with ethyl 2-bromomethylacrylate and activated zinc gave the α,β-unsaturated lactones 33 with an exocyclic double bond in mediocre yield. An analogue with an endocyclic double bond, the fungicidal sugar butenolide 35, was obtained by opening of epoxide 34 with the dilithium salt of phenylselenoacetic acid and subsequent oxidative elimination. The selectivities of the intramolecular nitrone cycloaddition reactions of 3-O-allyl-D-glucofuranose and 3-O-allyl-D-allofuranose derivatives 36 and 37, respectively, to give oxepans 38 and/or pyrans 39 have been investigated (see Vol. 27, Chapter 18, Scheme 1).

The C-disaccharide 43 (2-deaminotunicamycin) and its 7-epimer have been synthesized by addition of the 6-deoxy-6-diazo-D-galactose derivative 40 to aldehyde 29, followed by LiBHEt3-reduction of the ketone 41 and epoxide 42 thus obtained as a separable mixture (Scheme 6). The preparation of the first pseudo-C-disaccharide by use of the alkenyllithium compound derived from dibromoalkene 44 is covered in Chapter 18.

2.3.2 Chain-extension at the Reducing End. – Two-carbon Wittig elongation of 3,4:5,6-di-O-isopropylidene-aldehydo-D-glucose gave adduct 45, which on Mitsunobu inversion at C-4, hydrogenation of the double bond and lactonization furnished the 4,5-dideoxy-D-manno-oct-1,4-lactone derivative 46, a synthetic KDO precursor. Anomeric spiroketals have been constructed by alkoxy radical promoted intramolecular hydrogen abstraction/cyclization, as depicted in Scheme 7. Similar procedures were used to prepare hexose-derived dioxaspiro[5.5]undecanes and pentose-derived dioxaspiro[4.4]nonanes.

The α-C-furanosylglycine derivative 47 was prepared in 37% overall yield by use of N-Boc-t-butyldimethylsilyloxypyrole as a masked glycine anion, as shown in Scheme 8. Condensation of 4,6-O-benzylidene-D-glucose with nitroethane in the presence of DBU and 2-hydoxypyridine as 1,3 proton transfer catalyst gave, after reduction, the (α-aminoethyl) β-D-C-glucoside derivative 48. Further C-disaccharides are referred to in Chapter 3.

Application of the intramolecular nitrone-olefin cycloaddition to 3-O-allyl-D-glucose derivatives 49 and 50 and their D-allo isomers 51 and 52 furnished pyranoisoxazolidines 53 with varying degrees of diastereoselectivity. The main product obtained from 50 gave 54 on trimming of the side chain.

3 Physical Measurements

The nature of the relaxation process in supercooled, glassy carbohydrates has been examined by differential scanning calorimetry and dielectric relaxation measurements at 77-400 K over the frequency range 10-6 -10-3Hz. A gravimetric method during desorption of water has been used to determine the mean diffusion coefficients for maltose-water mixtures close to the glass transition temperature Tg. The effects of water structure enhancers (ethanol, tetramethylammonium chloride) and water structure breakers (urea, guanidine hydrochloride) on the stability of concentrated sucrose solutions have been studied by polarimetry and ion chromatography, and the attractive interaction between saccharides and monolignols has been estimated by measuring the solubilities of p-coumaryl-, coniferyl- and sinapyl-alcohol in aqueous solutions of D-glucose, D-galactose, D-mannose and D-xylose. The apparent association constant Kapp for coniferyl alcohol, for example, followed the order Xyl > Man > Gal > Glc.

4 Isomerizatioo

Examples of enzymic epimerization are given in Refs. 22 and 23 above.

5 Oxidation

The mechanism of the oxidation of D-glucose in alkaline solution on single crystal platinum electrodes has been investigated. A process for the preparation of D-arabinose from sodium D-gluconate in an electrochemical reactor with a fluidized bed electrode has been developed.

The oxidation of D-glucose to D-gluconic acid by molecular oxygen has been performed with bismuth-containing palladium-on-charcoal in water, with palladium-on-alumina in weakly basic media, and with sodium nitrite as catalyst in strongly acidic solution. The low temperature oxidation of non-reducing sugars (methyl D-glucosides, sucrose) and alditols (glucitol, mannitol) by oxygen in alkaline media has been studied in the presence of various catalysts, such as Cu(II) salts. The global kinetics of the ‘classical’ and of the anthraquinone-2-sulfonate catalysed alkaline oxidative degradation of lactose and related carbohydrates have been described. A reliable liquid chromatographic method for monitoring the oxidation of saccharides by oxygen in alkaline solution is referred to in Chapter 23.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 29 by R.J. Ferrier. Copyright © 1997 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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