Carbohydrate Chemistry Volume 9

A Review of the Literature Published During 1975

By J. S. Brimacombe

The Chemical Society

Copyright © 1977 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-082-4

Contents

Part I Mono-, Di-, and Tri-saccharides and their Derivatives,
1 Introduction, 3,
2 Free Sugars, 5,
3 Glycosides, 10,
4 Ethers and Anhydro-sugars, 28,
5 Acetals, 35,
6 Esters, 40,
7 Halogenated Sugars, 54,
8 Amino-sugars, 60,
9 Hydrazones, Osazones, and Related Compounds, 69,
10 Miscellaneous Nitrogen-containing Compounds, 71,
11 Thio- and Seleno-sugars, 77,
12 Derivatives with Nitrogen, Sulphur, or Phosphorus in the Sugar Ring, 81,
13 Deoxy-sugars, 86,
14 Unsaturated Derivatives, 91,
15 Branched-chain Sugars, 99,
16 Aldehydo-sugars, Aldosuloses, Dialdoses, and Diuloses, 107,
17 Sugar Acids and Lactones, 111,
18 Inorganic Derivatives, 120,
19 Cyclitols, 124,
20 Antibiotics, 131,
21 Nucleosides, 139,
22 Oxidation and Reduction, 168,
23 N.M.R. Spectroscopy and Conformational Features of Carbohydrates, 173,
24 Other Physical Methods, 185,
25 Polarimetry, 190,
26 Separatory and Analytical Methods, 192,
27 Alditols, 197,
28 The Synthesis of Optically Active Non-carbohydrate Compounds, 200,
Part II Macromolecules,
1 Introduction, 207,
2 General Methods By R. J. Sturgeon, 208,
3 Plant and Algal Polysaccharides By R. J. Sturgeon Starch Cellulose, 218,
4 Microbial Polysaccharides By R. J. Sturgeon, 237,
5 Glycoproteins, Glycopeptides, and Animal Polysaccharides By B. J. Catley, 272,
6 Enzymes By J. F. Kennedy, 327,
7 Glycolipids and Gangliosides By R. J. Sturgeon, 397,
8 Chemical Synthesis and Modification of Oligosaccharides, Polysaccharides, Glycoproteins, Enzymes, and Glycolipids By J. F. Kennedy, 412,
Author Index, 463,

CHAPTER 1

Introduction

The general terms of reference remain those set out in the Introduction to Volume 1 (p. 3) and the arrangement of subject matter follows that of previous Reports in this Series.

Calcium and strontium salts have been used to alter the anomeric equilibria in the Fischer glycosidation of several aldoses, so allowing glycosides not normally obtained (e.g. methyl α-D-ribofuranoside, β-D-lyxo-furanoside and -pyranoside, α-D-talopyranoside, α- and β-D-talofuranosides) to be isolated (Chapter 3). Conditions necessary for successful halide-catalysed glycosidations have been defined by Lemieux and applied to the synthesis of several tri-saccharides of biological importance (Chapter 3). A good deal of interest has also been shown in the synthesis of C-glycosides, much of it centred on the elaboration of C-glycosyl nucleosides of biological interest (see Chapters 3 and 21).

A point made again in Chapter 6 is that assessment of the relative reactivities of hydroxy-groups in sugars based on product distributions can lead to erroneous conclusions, since the reactivity of a hydroxy-group can change during the course of a multistage reaction.

The customary interest has been shown in unusual naturally occurring sugars, and syntheses of ristosamine (Chapter 8), axenose, and pillarose (Chapter 15) have been reported. Following the synthesis of derivatives of dihydrostrepto-mycin in 1974, Umezawa’s group has now reported the total synthesis of streptomycin (Chapter 20). A combination of chemical and spectroscopic methods has been used to good effect in unravelling the highly intricate structures of such carbohydrate-containing antibiotics as everninomycin D (a truly monumental achievement!), the destomycins, hikizimycin, and several gentamycins and aldgamycins (Chapter 20). The bourgeoning activity in nucleoside chemistry is demonstrated by the fact that Chapter 21 contains roughly one-seventh of the total references appearing in Part I of this Report.

Although references to the use of carbohydrates in the total synthesis of optically active non-carbohydrate compounds have been included in previous Reports, they were usually scattered throughout several chapters. Because of the growing interest in using carbohydrates in this way, such references have been collected together in a new chapter at the end of Part I.

Some aspects of the chemistry of unsaturated sugars have been reviewed, and several books of general interest have appeared over the past year.

The December issue of Carbohydrate Research was dedicated to the memory of Dr. Hewitt G. Fletcher, jun. (1917 — 1973), and the March issue was dedicated to Professor Michael Heidelberger to mark his distinguished contributions to carbohydrate chemistry.

CHAPTER 2

Free Sugars

Browning reactions of sugars have been reviewed, and the results of tests of Shallenberger’s hypothesis relating the structure of sugars to their sweetness are reported in Chapter 4.

Isolation and Synthesis

D-[5-3H]Xylose has been synthesized from the pentodialdose (1) by reduction with sodium borotritide, followed by removal of the protecting group. D-Allose and D-altrose were obtained in comparable amounts (45 : 55 parts) from D-ribose by the nitromethane route, the overall yield being 42%. Molybdate-catalysed epimerization raised the proportion of D-allose to 60%, in contrast to other epimerizations where epimers with O-2 and O-3 trans-related are preferred. Epimerization of a D-gulo-compound at C-2 was used to prepare 1,2,3-tri-O-acetyl-5,6-di-O-benzoyl-D-idofuranose (2) (Scheme 1); the usefulness of this approach lies in the formation of a D-idofuranose derivative, rather than as a synthetic route to the free sugar. L-Sorbose found in apple-cider vinegar appears to be formed by oxidation of D-glucitol, since it is not originally present in the cider.

Application of the nitromethane route to L-mannose has furnished a mixture of L-glycero-L-galacto-heptose (43%) and L-glycero-L-talo-heptose (12%), which could be separated by ion-exchange chromatography. A synthesis of D-gluco--hept-3-ulose (4) from perseitol (3) is shown in Scheme 2; the racemic form of (4) was similarly obtained from the meso-heptitol (5). The following octuloses have been shown to accumulate when the leaves of red clover (Trifolium pratense) were allowed to imbibe solutions of the pentoses and hexoses indicated: L-glycero-L-galacto--octulose (L-arabinose or L-mannose), D-glycero-D-galacto-octulose (D-xylose or D-gulose), and D-glycero-D-altro-octulose (D-ribose or D-allose).

Physical Measurements

Although aqueous solutions of D-xylose and D-glucose contain insignificant proportions of furanose forms, 1H n.m.r. spectroscopy has indicated that ~ 15% of the β-furanoses are present in the tautomeric equilibria of the corresponding 3-O-methyl ethers; these equilibria are not governed by stereochemical factors alone, and solvation effects may be important. The rate constants for the forward and reverse reactions in the mutarotation of α-D-glucopyranose in 70% p-dioxan have been determined. The rate of crystallization of lactose has been related to the rate of cooling and to the rate constants for mutarotation. The complex mutarotation shown by some monosaccharides has been analysed mathematically based on a scheme of three components; detailed analysis of D-galactose showed that the slow and fast processes of the complex mutarotation correspond approximately to pyranose-pyranose and pyranose-furanose inter-conversions, respectively. The ionization and mutarotation of hexoses in aqueous alkaline solution have been examined using C n.m.r. spectroscopy; the rate-determining step in mutarotation is the rotation about the C-1 — C-2 bond of the acyclic intermediate. The β-anomer is the more acidic D-gluco-pyranose, whereas the reverse holds for the D-mannopyranoses, indicating that an eq.-ax. sequence of the anomeric and adjacent hydroxy-groups is less favourably disposed towards ionization than either ax.-ax. or eq.-eq. sequences. Related studies have used i.r. spectroscopy to follow the reaction of β-D-glucopyranose with hydroxide ions.

Two groups have used physical measurements (e.g. density, viscosity, refractive index, and optical rotation) to determine the compositions of solutions of water-sucrose-D-glucose (or invert sugar) at various temperatures. The diffusion coefficient for self-diffusion of D-fructose in an aqueous system has been measured over a range of concentrations and temperatures. The yields of trapped electrons and radicals have been determined following γ-irradiation of frozen aqueous solutions of sugars.

The alkali-catalysed reactions of trioses (glyceraldehyde and dihydroxyacetone) have again been investigated, but this time using a pH-stat to maintain a constant concentration of the catalyst and employing a polarographic method to determine the concentration of triose. The preferred course of aldolization, giving such products as fructose, sorbose, and dendroketose, depends on the reaction conditions, especially the concentration of triose. The kinetics and mechanism of aldolization were partly elucidated.

Oxidation of seven aldoses by vanadium(v) in sulphuric acid or perchloric acid has been examined by kinetic methods [for studies with cerium(iv) see J. Org. Chem., 1974, 39, 1788]. It was concluded that the rates correlate with the proportions of aldehydo-forms present, although this may really mean the relative rates of attainment of the aldehydo-iorms; the observed order of rates, arabi-nose = xylose > galactose > mannose > glucose, is consistent with this view. Other workers have studied the kinetics and mechanism of oxidation of a number of free sugars by silver© in the presence of ammonium hydroxide; the inter-mediacy of an ene-diolate anion was suggested, since the rates of oxidation were effectively the rates of enolization of the sugars. Related studies on the oxidation of D-sorbose with chloramine-T in highly alkaline solution have been reported. Only two species, D-glucose. B4 O72- and free D-glucose, have been found to be involved in a polarimetric titration of D-glucose by tetraborate (B4O72-), but no bis(bidentate) species [(D-glucose)2. B4O72-] was detected. LCAO calculations have been used to provide information on the electronic configurations of D-glucopyranose, D-glucofuranose, and aldehydo-D-glucose and its hydrated form; dipole moments for α- and β-D-glucopyranose were calculated.

Reactions

Labelling studies have established that intramolecular hydride-transfer occurs from C-2 to C-1 during the acid-catalysed isomerization of hexoses; thus, D-[23H]glucose afforded D-[1-3H]fructose containing equal proportions of the R- and S-forms. The reaction is similar to the enzyme-catalysed, but not to the base-catalysed, isomerization.

Deuterium-labelled derivatives of D-glucose have been used in a 1H n.m.r. spectroscopic study of the action of alkali on carbohydrates; it appears that degradation of 3-O-methanesulphonyl-D-glucose does not involve H-1. Cyclo-pentane-1,2-dione has been detected among the products of alkaline degradation of a number of carbohydrates. In addition to minor amounts of pentose, tetrose, and triose derivatives, γ-radiolysis of D-glucose in aerated aqueous solution yielded D-glucono-1,5-lactone, D-arabino-hexosulose, D-ribo-hexos-3-ulose, D-xylo-hexos-4-ulose, and D-xylo-hexos-5-ulose by the overall reaction shown in Scheme 3. Among the products identified on γ-radiolysis of D-glucose in deoxygenated aqueous solutions saturated with nitrous oxide were D-gluconic acid, hexuloses, dialdoses, and lower sugars. The oxidation of D-xylose in acidic solutions containing transition-metal ions has been studied; eight carboxylic (oxalic, glycolic, glyceric, maleic, fumaric, tartaric, pyromucic, and formic) acids and carbonic acid were formed in the presence of cupric sulphate, whereas ferric sulphate, mercuric nitrate, and eerie sulphate gave principally oxalic acid, D-xylonic acid, and formic acid, respectively. A radical mechanism has been proposed for the oxidation of reducing sugars by oxygen in alkaline solutions.

Differential thermal and thermogravimetric analyses have been used to study the pyrolysis of pentoses. An examination of the influence of agar-agar, sucrose, lactose, and sodium chloride on the rate of crystallization of D-glucose at 40 °C showed that sodium chloride has the largest retarding effect; the effects of other organic and inorganic additives were also reported.

In continuing their work on the transport of sugars across the human-erythro-cyte membrane, Barnett and his co-workers have shown that D-glucose inhibits the transport of 6-O-methyl-D-galactose, indicating that both sugars utilize the same sugar-transport system. The protection that various substituted hexoses afforded against deactivation of the sugar-transport system by fluorodinitro-benzene was also examined, and a mechanism for the transport of sugars across the membrane was suggested. The mechanism of inhibition of D-glucose transport in a Neurospora species by arsenate has also been studied. The degradation of D-xylose by a pseudomonad is referred to in Chapter 17.

CHAPTER 3

Glycosides

O-Glycosides

Calcium and strontium salts can be used advantageously in the Fischer synthesis of methyl α-D-ribofuranoside, methyl β-D-lyxo-furanoside and -pyranoside, methyl α- and β-D-mannofuranoside, methyl α-D-talopyranoside, methyl α- and β-D-talofuranoside, methyl α-L-gulo-furanoside and -pyranoside, and the methyl D-glycero-D-gulo-heptosides. The glycosides from preparative glycosidations were conveniently separated on cation-exchange resins in the Ca2+ or Sr2+ forms. The use of metal ions in glycosidations can result in the formation of significant proportions of dimethyl acetals (see Chapter 5).

Treatment of L-fucose with methanolic hydrogen chloride has been shown to yield a final equilibrium mixture containing methyl α-L-fucofuranoside (6%), methyl β-D-L-fucofuranoside (13%), methyl α-L-fucopyranoside (54%), and methyl β-L-fucopyranoside (27%). Both L-fucopyranosides and both L-fucofuranosides are formed simultaneously in the early stages of the reaction, in contrast to the initial formation of the β-furanoside and the α-pyranoside on similar treatment of D-galactose. Methanolysis of a number of D-glucose-containing disaccharides has shown that they react initially at the reducing-end, whereafter cleavage of the inter-saccharide linkage furnishes D-gluco-furanosides and -pyranosides.

Methanolysis of α-lipomycin afforded the α- and β-furanosides and α- and β-pyranosides of 2,6-dideoxy-D-ribo-hexose in the proportions 12.5 : 12.5 : 25 : 50.

Direct glycosidation of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose with alcohols in the presence of silver trifluoromethanesulphonate, 4-nitrobenzenesulphonyl chloride, and triethylamine afforded the β-glycosides in reasonable yield. The use of 2,3:4,5-di-O-isopropylidene-D-glucose in the preparation of the methyl D-glucoseptanosides is reported in Chapter 5.

Lemieux’s group have reviewed the theoretical aspects pertaining to displacements at the anomeric centre of sugars, and have defined the following criteria for successful halide-catalysed glycosidations yielding α-glycosides from derivatives of glycosyl halides: (i) the concentration of halide ion must ensure that anomerization of the glycosyl halide is faster than the displacement of the less reactive α-halide by the alcohol; (ii) the halide must react with the alcohol without assistance from metal ions or highly polar solvents; and (iii) the reaction conditions should minimize side-reactions involving the loss of protecting groups or the formation of glycosidic products other than the desired α-glycoside. Based on these considerations, several α-linked disaccharides were synthesized in good yield and in a highly stereoselective manner by reaction of perbenzylated α-D-gluco-, α-D(L)-galacto-, and α-L-fuco-pyranosyl bromides with suitably protected derivatives of D-glucose and D-galactose in the presence of tetraethylammonium bromide; e.g. 6-O-α-D-glucopyranosyl -D-galactose, 3-O-α-D-glucopyranosyl-D-glucose, and 3-O-α-D-galactopyranosyl-D-galactose were among the disaccharides synthesized. The synthesis of the Lea blood-group antigenic determinant, O-(α-L-fucopyranosyl) -(1 [right arrow] 4)-[O-(β-D-galactopyranosyl)-(1 [right arrow 3)]-2-acetamido-2-deoxy-D-glucose, was described in the succeeding paper; the key glycosylation step is shown in Scheme 4. An isomeric 6-O-L-fucopyranosyl analogue of the trisaccharide was also obtained in this reaction, the isomers being distinguished by 13C n.m.r. spectroscopy. Another paper reported the synthesis of O-(α-L-fucopyranosyl)-(1 [right arrow] 2)-[O-(α-D-galactopyranosyl)-(1 [right arrow] 3)]-D-galactose, which forms part of the antigenic determinant of blood-group B substance. One of the key steps in the synthesis of this trisaccharide is illustrated in Scheme 5; the D-galactopyranoside derivative (6) is an important intermediate in the synthesis of the disaccharide derivative used, since, after glycosylation, the 3,4-O-isopro-pylidene group was replaced by a 3,4-O-(ethoxyethylidene) group, which was converted into the corresponding axial 4-acetate on partial hydrolysis with acid. Finally, Lemieux’s group have prepared β-glycosides of O-(α-L-fucopyranosyl)-(1 [right arrow] 4)-[O-(β-D-galactopyranosyl)-(1 [right arrow] 3)]-2-acetamido-2-deoxy-D-glucose using either 8-ethoxycarbonyl- or 8-methoxycarbonyl-octanol. Semisynthetic antigens were prepared from these esters by attachment to the free amino-groups in bovine serum albumin. Antibodies raised with the trisaccharide antigen precipitated blood-group Le substance and agglutinated Le red-blood cells.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 9 by J. S. Brimacombe. Copyright © 1977 The Chemical Society. Excerpted by permission of The Chemical Society.
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