Carbohydrate Chemistry Volume 28

A Review of the Literature Published during 1994

By R. J. Ferrier

The Royal Society of Chemistry

Copyright © 1996 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85404-208-1

Contents

Chapter 1 Introduction and General Aspects, 1,
Chapter 2 Free Sugars, 3,
Chapter 3 Glycosides, 19,
Chapter 4 Oligosaccharides, 64,
Chapter 5 Ethers and Anhydro-sugars, 85,
Chapter 6 Acetals, 94,
Chapter 7 Esters, 100,
Chapter 8 Halogeno-sugars, 115,
Chapter 9 Amino-sugars, 120,
Chapter 10 Miscellaneous Nitrogen Derivatives, 137,
Chapter 11 Thio- and Seleno-sugars, 158,
Chapter 12 Deoxy-sugars, 165,
Chapter 13 Unsaturated Derivatives, 170,
Chapter 14 Branched-chain Sugars, 181,
Chapter 15 Aldosuloses and Other Dicarbonyl Compounds, 197,
Chapter 16 Sugar Acids and Lactones, 199,
Chapter 17 Inorganic Derivatives, 214,
Chapter 18 Alditols and Cyclitols, 219,
Chapter 19 Antibiotics, 251,
Chapter 20 Nucleosides, 263,
Chapter 21 N.M.R. Spectroscopy and Conformational Features, 307,
Chapter 22 Other Physical Methods, 318,
Chapter 23 Separatory and Analytical Methods, 333,
Chapter 24 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds, 345,
Author Index, 380,

CHAPTER 1

Introduction and General Aspects

A description of the pioneering work of Emil Fischer in the period around 1890, especially relating to his elucidation of the molecular configuration of glucose and aspects of his philosophical view of chemistry, has appeared. Lemieux and Spohr have looked in detail at how Fischer was led to the “lock and key” concept for enzyme specificity. An animated 386-based PC program with VGA graphics has been produced to assist visualization of the relationship between Fischer and Haworth projections of monosaccharides.

An ACS symposium was held in 1993 on the anomeric effect and associated stereoelectronic effects, and as part of it J. T. Edward reviewed the influence of the anomeric effect in carbohydrates covering the origin of its postulation. Several calculations relevant to carbohydrates have been reported. Ab initio M.O. methods have been applied to the axial and equatorial conformations of 2-methoxytetrahydropyrans, and also 2-chloro- and 2-fluoro-tetrahydropyrans, the energy values obtained being found to be dependent on solvent. Force fields have been calculated for monosaccharides and (1 -> 4)-linked polysaccharides, and a review has been written on path energy minimization (PEM), a novel method for generating a reaction path linking two known conformations of molecules. A test example considered the change in pucker angle of α-D-threo-pentulofuranose. The method can identify transition state structures and energy barriers. A major review covering structural and conformational analysis of oligosaccharides of glycoproteins deals with n.m.r., mass spectrometric and molecular modelling methods.

Considerable attention has been given in reviews to aspects of synthesis. The question of reactions which are promoted by water has been dealt with covering i) Diels Alder and hetero-Diels Alder reactions by which nionosaccharides may be synthesized; ii) sigmatropic rearrangements of aglycons which lead to asymmetric induction; iii) indium promotion of allylation of aldehydes or ketones and iv) reductive debrominations using soluble tin hydrides and AIBN. A further review has dealt with the hetero-Diels Alder reaction in asymmetric systems, and covered the use of carbohydrate chiral auxiliaries and the construction of pyranose rings from sugar butadien-1-yl ethers. The trichloroacetirnidate method for making glycosides which has become well established as of major importance has been reviewed by the developer, R. R. Schmidt, and the use of aldonolactones in synthesis has covered O-substitution and deoxygenation, reactions with various nucleophiles including chain elongating reagents, reductions and β-eliminations. Tetrapropylammoniwn perruthenate has become recognized as a soluble, non-volatile, stable oxidising agent for converting alcohols to ketones; used with sodium hyperchlorite it cleaves a-diols, and its chemistry has been reviewed.

New aspects of the synthesis of glycopeptides which contain glycosyl asparagine, serine and threonine has covered O– and N-glycosylations, and dealt with enzymic and solid phase procedures. A review of the use of enzymic methods in protecting group technology includes cover of examples relating to carbohydrates and nucleosides, and a further relates to chemoenzymic methods for preparing derivatives of D-ribose containing one or more 13c labels.

CHAPTER 2

Free Sugars

1 Theoretical Aspects

The relevant literature on lactose dissolution in water has been reviewed in a paper which describes a mathematical model for this process. Short time scale molecular dynamics simulations of sucrose in water and DMSO indicated that the conformations in both solvents are similar to that accepted in the crystalline state. Solid-liquid equilibria for aqueous sucrose have been studied by use of an UNIQUAC model. A comparison of GROMOS force field and Ha force field in molecular dynamics simulations of glucose crystals indicated superior performance by the latter method. Predicted crystal structures of β-D-glucose, β-D-galactose, β-D-allose, α-D-glucose, α-D-galactose, and α-D-talose matched or nearly matched the X-ray-derived data in four cases.

2 Synthesis

The synthesis of aldose derivatives by iterative, diastereofacially selective addition of 2-lithio-1,3-dithiane to O-protected chiral α-hydroxyaldehydes, starting from 1,2-O-cyclohexylidene-D-glyceraldehyde, has been reported. In a new modification of the aldolase-catalysed synthesis of ketose phosphates (see Vol. 27, Chapter 7, Ref. 71) the required dihydroxyacetone phosphate (DHAP) has been generated in situ from glycerol 1-phosphate by use of glycerol phosphate oxidase coupled with catalase. A large number of ketosugars, for example the new fluorinated [D]-fructose derivative 1, have been prepared by addition of the one-carbon nucleophile (benzyloxymethyl)lithium to suitably substituted and protected aldono-1,4-lactones. Acetyl-protected free pento-, hexo- and hepto-furanoses, such as compounds 2, have been obtained by reduction of the corresponding 1,4-aldonolactones with disiamylborane. An interesting new approach to chiral precursors of C-3 branched alditol and aldose derivatives involving bis-epoxidation of silylated ketenes is covered in Chapter 18, and the oxidative degradation of galactose, lactose, cellobiose and maltose to the next lower aldoses by hydrogen peroxide in the presence of borate ions is referred to in Section 5 of this Chapter (Ref 83).

2.1 Trioses to Hexoses. – Mixtures of erythro– and threo-3-pentulose have been obtained in the base-catalysed aldol condensation between unprotected DL-glycero-tetruose and formaldehyde, the product ratio depending on catalyst and solvent. In further studies on the aldolization of glycolaldehyde derivative 3, use of lithium hydroxide as catalyst furnished DL-galactose as the major trimerization product in 7.5% yield, in contrast to previous experiments with NaOH or KOH which had produced allose as the main hexose (see Vol. 25, Chapter 2, Ref. 12).

In the transketolase-catalysed condensation (see Vol. 27, Chapter 2, Refs. 6, 16) of hydroxypyruvate with a mixture of all four 4-deoxytetrose isomers, only the 2R-isomers reacted and only products with S-stereochemistry at the new chiral centre (C-3), i.e., 6-deoxy-D-fructose and 6-deoxy-L-sorbose, were formed. A preparation of D- and L-fluctose by enzymic aldol condensation is referred to below (Ref. 23), and the enzymic conversion of D- and L-erythro-pentulose, D-tagatose and D-psicose to the corresponding 3,4-threo-compounds is covered in Part 4 of this Chapter (Ref. 65).

Oxidation/reduction at C-2 was used to convert the 4,6-O-Tips-protected methyl α-L-arabinoside 4 to the corresponding L-ribose derivative 5. Preferential secondary oxidation of 3,4-di-O-benzyl-D-mannitol with ibis(tributyltin) oxide and bromine gave 3,4-di-O-benzyl-D-fluctose in 87% yield. Efficient new syntheses of methyl α-D-allopyranoside and methyl 3-deoxy-α-D-ribo-hexopyranoside relied on the selective enzymic acylation at the 2-position of methyl α-D-glucopyranoside derivative 6 to give 7, which was subjected to oxidation/reduction and to deoxygenation, respectively.

A new synthesis of L-talose from D-glucose, which is outlined in Scheme 1, involved inversion of configuration by oxidation/reduction at C-3 and sulfonate displacement at C-5. The L-talose was used for making new furanosyl- and pyranosyl-adenine nucleosides. A preparation of L-gulose from D-mannose, incorporating as the key-step inversion at C-5 in an acyclic intermediate, is shown in Scheme 2. The β-fragmentation/cyclization of carbohydnice anomeric alkoxy radicals, a novel method of descending the aldose series (see Vol. 27, Chapter 2, Refs. 12, 13) has been applied to the preparation of pentoses from hexoses. Iodine and diphenylselenium hydroxyacetate, a stable and readily available crystalline compound, were used u reagents instead of iodosobenzene.

A practical method for the gram-salt preparation of D-[5-2H]glucopyranese in 7 steps and 15% overall yield from diacetone glucose has been developed. The label was introduced by stereoselective reduction of the known ketone 8 with sodium borodeuteride. Various methods were employed to synthesise D-[1-2H]-, D-[4-2H]-, D-[5-2H2]-, D-[(5R)-2H]- and D-[(5S)-2H]-ribose and thence specifically labelled 4-N-benzoylcytidines and, by deoxygenation, 2′-deoxy analogues. D-[6-11C]Glucose has been obtained from protected α-D-xylo-pentodialdo-1,4-furanose by use of a 11CH3I-derived Wittig reagent.

Selective cleavage of either diastereomer of phenyl or 4-nitrophenyl β-D-glucopyranosyl sulfoxide to give the free sugar has been achieved with β-glucosidases of various origins.

2.2 Chain-extended Compounds.-Higher sugars have been produced by osmylation of known heptenoses and oct-dienoses. The rhamnulose 1-phosphate aldolase-catalysed condensation of DHAP (see Vol. 25, Chapter 7, Ref. 44) with aldehydes 9, obtained by asymmetric dihydroxylation, gave after phosphatase treatment L-fructose (10), 6-C-phenyl-D-galacto-2-hexulose (11) or 7-deoxy-D-galacto-2-heptulose (12), i.e., products with 3R/4S/5S/(6R)-stereochemistry, as shown in Scheme 3. The enantiomers of the three uloses were obtained by use of the hydroxylation auxiliary with the opposite chirality and fructose diphosphate aldolase as condensation catalyst.

2.2.1 Chain-extension at the “Non-reducing End”. – Dialdoses were again the substrates in a number of chain-elongations, by one to four carbons. The versatile LD-Hepp derivative 14 was the main product (63%) from the Grignard addition of allyloxymethylmagnesium bromide to hexodialdo-1,5-pyranoside 13. A similar synthesis using (dimethylphenylsilyl)methylmagnesium chloride followed by peracetic acid, that gave product 16 from starting compound 15 in comparable yield, has also been reported. The conversion of LD-Hepp derivative 16 to its DD-isomer is referred to in Chapter 7. In the presence of metal ions, (dimethylphenylsilyl)methyl magnesium chloride reacted stereoselectively with the benzylimino compound 18, obtained by exposure of 17 to benzylamine. Cerium(III) chloride and copper(I) iodide promoted the preferred formation of the syn– and anti-adducts 19 and 20, respectively. The latter is a precursor of lincosamine. The 2-trimethylsilylthiazole homologation of the dibenzyl ethers 21 was non-selective (in contrast to that of 17, see Vol. 27, Chapter 2, Ref. 20) as was oxidation/reduction of the addition products 22. However, oxidation/L-selectride reduction of the deprotected, reduced, and 7-O-silylated products gave mainly the required D-glycero-D-gluco-(or manno)-heptopyranosides 23; access to the methyl pyranoside of D-glycero-D-altro-heptose, a constituent of the O-antigen chains in certain lipopolysaccharides, was provided by epimerization at C-2 and C-3 of 23avia the derived 2,3-D-glycero-D-allo-epoxide.

Two-carbon chain-extension by condensation of α-D-lyxo-pentodialdo-1,4-furanose derivative 24 with the anion formed from the acetyliron complex 27 gave a 2:1 mixture of products 25. Decomplexation with NBS in methanol furnished the separable methyl uronates 26. Two methods for three-carbon elongation, both using thiazole based reagents, are illustrated in Scheme 4. As the Wittig route was complementary, in stereochemical tenns, to the enolate route and selective reduction of ketones 28 and 29 was readily achieved by choice of appropriate reaction conditions, all four stereoisomers 30 were available.

Sugar allyltin derivatives, convenient precursors of dienoaldehydes such as compounds 31, have been obtained by SR2 reaction of trialkyltin radicals with allylic thiocarbonates which were, in turn, produced by Wittig condensation followed by a 3:3 thermal rearrangement, as shown in Scheme 5.

In a further development of the aldolase-catalysed synthesis of sugars (see Ref. 4 above), both DHAP (33) and the aldehyde component 35 were generated in situ from glycerol 1-phosphate (32) and methyl β-D-galactopyranoside (34), respectively, by microbial oxidation. Use of rhamnulose 1-phosphate aldolase caused formation of a single nonose-8-ulose 36 (which underwent intramolecular hemiacetal cyclization) with the expected L-threo-stereochemistry across the new carbon-carbon bond (Scheme 6). A new synthesis of N-acetylneuraminic acid derivatives and analogues involved as the key-step reaction of dialdose derivative 37 with the Wittig reagent 39 to give non-5-enose derivative 38 in 76% yield.

One carbon elongation has also been achieved by displacement of primary triflate groups with potassium cyanide, and by opening of 5,6-epoxide 40 with 2-lithio-2-trimethylsilyl-1,3-dithiane to form 41 which on exposure to mercury(II) perchlorate gave acylsilane 42. Displacement of primary iodide by propyl nitrite accompanied by displacement/cyclization of secondary tosylate opened a route to optically pure 4-oxygenated 4,5-dihydroisoxazoles 43. These compounds are potentially useful intermediates for further chain-extensions (Scheme 7).

C-6-Allylated pyranoses and C-5-allylated furanoses were prepared from the corresponding iodides by Keck radical coupling with allyltributyltin (e.g. 44 -> 55). The selective formation of product 47 in the chain-extension of the acetal-protected uronic acid derivative 46 by radical addition of methyl acrylate using Barton’s method was ascribed to addition from the less hindered side to a conformationally stable radical intermediate; the peracetate 48 furnished a 1:1 mixture of 49 and 50.

Cycloaddition of nitrite oxides to the D]-lyxo-alkene 51 gave mainly the C-4/C-5-erythro-adducts 52 (see Vol. 25, Chapter 10, Refs. 91,92). The nitrite oxide-isoxazoline route involving sugar-derived nitrite oxides as well as sugar-derived alkenes (see Vol. 27, Chapter 2, Ref 39) has been applied to the synthesis of a 6-deoxy-dodecoses and a 7-deoxy-tridecoses. Sugar β-ketophosphonates have been employed in the synthesis of higher sugars. An example is Scheme 8. Use of a C12-dialdose and a C9-sugar ketophosphonate in a similar condensation gave an unsaturated C21-sugar.

“C-Ribosylhopane” (54), a postulated bio-precursor of the bacteriohopanepolyols, was synthesized from the triolamine 53 by O-silylation and oxidation of the amine with dimethyldioxirane, followed by deprotection.

2.2.2 Chain-extension at the Reducing End. – Partially protected D-gluco-, D-allo-, and L-rhamno-pyranose have been converted in moderate yields to heptonic acid δ-lactones by Kiliani ascent. Several 2,6-anhydroheptoses have been prepared by ozonolysis of the corresponding sodium 2,6-anhydro-1-deoxyheptitol-1-nitronates.

The tin- and indium-mediated allylation of unprotected carbohydrates in aqueous media has been reviewed. The recent application of this methodology to the conversion of D-arabinose to D-glycero-D-galacto-heptose (55) in eight steps and 30% overall yield is shown in Scheme 9. A route to the bicyclic octose derivative 56, required for the synthesis of the octosyl nucleoside moiety of the antibiotic ezomycin A1, is outlined in Scheme 10.

A powerful strategy for chain-extension by 7 carbon atoms using consecutively two Horner-Emmons condensations and addition of a silyloxyallylic stannane, and involving highly stereoselective osmylation of three double bonds is illustrated in Scheme 11. The selectively protected D-manno-D-manno-D-arabino derivative 57 was obtained with excellent diastereoselectivity; regioselective diol cleavage furnished lactol 58.

The synthesis of sphingosine from 2,4-O-benzylidene-D-threose was hampered by failure to achieve arabino-selectivity in the addition of tetradecosylmagnesium bromide as well as in the oxidation/reduction of the resulting mixed alcohols by all methods tried except the samarium iodide-assisted Tishchenko reaction.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 28 by R. J. Ferrier. Copyright © 1996 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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