Carbohydrate Chemistry Volume 25

Monosaccharides, Disaccharides, and Specific Oligosaccharides

By R. J. Ferrier

The Royal Society of Chemistry

Copyright © 1993 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-692-5

Contents

Chapter 1 Introduction and General Aspects, 1,
Chapter 2 Free sugars, 3,
Chapter 3 Glycosides, 15,
Chapter 4 Oligosaccharides, 64,
Chapter 5 Ethers and Anhydro-sugars, 79,
Chapter 6 Acetals, 85,
Chapter 7 Esters, 87,
Chapter 8 Halogeno-sugars, 104,
Chapter 9 Amino-sugars, 107,
Chapter 10 Miscellaneous Nitrogen Derivatives, 121,
Chapter 11 Thio- and Seleno-sugars, 136,
Chapter 12 Deoxy-sugars, 143,
Chapter 13 Unsaturated Derivatives, 151,
Chapter 14 Branched-chain Sugars, 161,
Chapter 15 Aldosuloses, Dialdoses, and Diuloses, 180,
Chapter 16 Sugar Acids and Lactones, 182,
Chapter 17 Inorganic Derivatives, 195,
Chapter 18 Alditols and Cyclitols, 199,
Chapter 19 Antibiotics, 224,
Chapter 20 Nucleosides, 242,
Chapter 21 N.M.R. Spectroscopy and Conformational Features, 282,
Chapter 22 Other Physical Methods, 293,
Chapter 23 Separatory and Analytical Methods, 305,
Chapter 24 Synthesis of Enantiomerically Pure Non-carbohydrate Compounds, 318,
Author Index, 339,

CHAPTER 1

Introduction and General Aspects

The steady advances reported in the 1991 literature show how well the subject connects basic aspects of organic chemistry with medical and biological science. Knowledge of the chemistry of glycosyl cations, anions, free radicals and carbenes has been taken forward on the one hand, and many syntheses have been reported that have been initiated by the needs of biologists, and biological (especially enzymic) methods as tools in synthetic carbohydrate chemistry have become overtly more accessible and useful.

Oligosaccharide syntheses and structural/conformational analyses by spectroscopic and theoretical methods have advanced appreciably and in line with the continuing increase in the recognition of these compounds as key elements of certain biological processes.

An appreciation of the life and work of the great Japanese medicinal chemist Hamao Umezawa has appeared.

Many articles of general interest and reviews on specific topics have been published in 1991. One describes a method for transferring Fischer projection formulae into zig-zag alternatives which should be of interest to those teaching the subject. Of more historical significance is a review of the evolution of the formulae used to depict sucrose, ranging from the earliest to those that are graphic displays which reveal the hydrophobic surfaces. A symposium report covers such topics as configurational and conformational assignments, comparison of solutions and solid state conformations, the orientations of substituent groups and conformational features of oligosaccharides. Related reviews have dealt with the current state of knowledge on the solution properties of low molecular weight polyhydroxy compounds including the influence of solvation on their dynamic characteristics, the stereochemical aspects of hydration of carbohydrates in aqueous solution as derived from density and ultrasound measurements, the role of lone-pair interactions in the chemistry of monosaccharide derivatives including unsaturated compounds, the use of the “prudent ascent” method in the conformational analysis of methyl cellobioside and the sweetener “trichlorogalactosucrose”, and molecular dynamics simulation of carbohydrates including conformational energy mapping of mono- and oligo-saccharides.

Special interest will be taken in the topic of association of resorcinol-aldehyde cyclotetramers and sugars in aqueous or non-aqueous media which has been reviewed (in Japanese).

In the area of synthesis, reviews have covered the use of carbohydrate in industrial chemical manufacture, the synthesis of long-chain sugars and branched compounds from furan derivatives, and the preparation of sugars by different methods as synthons for asymmetric synthesis.

A major review covering 203 references on the use of enzyme methods in sugar and oligosaccharide synthesis and acylations and deacylations has appeared. Others have focused on enzymic synthesis of sugars, oligosaccharides and sugar nucleotides’ and on enzymic methods for bringing about O-substitution and deprotection.

Vasella has reviewed the chemistry of glycosyl carbanions, carbocations, radicals and carbenes and related work covering his own important contributions and those of others.

Specific areas to have been reviewed are carba-sugars (with ring oxygen atoms replaced by carbon), the enediyne anticancer antibiotics notably calicheamycin and esperamycin (Nicolaou’s synthetic work on the disaccharide component especially).

Ally] sulphenates show promise as hydroxyl protecting groups. These are stable under conditions in which many types of groups are cleaved and may themselves be removed by Pd (0)-calalysed transfer (see Chapter 7).

Finally, a paper has been published on the therapeutic applications of various carbohydrate-based compounds.

CHAPTER 2

Free Sugars

1 Theoretical Aspects

An essay on the structural representation of sucrose has been published. Following an historical account of the establishment of the constitutional formula and conformational features of sucrose, the present possibilities for graphics displays of its molecular geometry, contact surfaces, and hydrophobicity potential are given.

Free energy simulations of the equilibrium between the α- and β-anomers of D-glucopyranose in aqueous solution have been described.

2 Synthesis

Two reviews on the use of furan-derived “naked sugars” in the synthesis of unusual carbohydrate derivatives (e.g., L-hexoses, higher carbon sugars) have been published, and recent developments in the synthesis of carbohydrates by means of microbial aldolase catalysis have been reviewed.

In continuation of earlier studies on the formose reaction in aqueous DMF catalysed by triethylamine and thiamine hydrochloride (see Vol.23, Chapter 2, ref. 13), the effects of changes in the concentration of either water, formaldehyde, or triethylamine on the product distribution have been examined.’ Improved yields of threo-3-pentulose (19% by g.l.c.) were obtained when the formose reaction was carried out in DMSO in the presence of Pb2O(OH) and thiamine hydrochloride.

Transketolase from spinach leaves has been used in the stereospecific condensation of hydroxypyruvic acid with a variety of aldehydes, including free sugars, which gives ketoses with (5) configuration at the new chiral centre. An example is given in Scheme 1.

1.1 Trioses – Hexoses. – Full details have been published on a high yielding bulk synthesis of O-isopropylidene-D-glyceraldehyde from D-mannitol.

Derivatives (3) of DL-threose and 4-deoxy-DL-threose are available from C-1 oxygenated allylic silanes (1) via α,β-dialkoxyacylsilanes (2) as shown in Scheme 2. The di- and tri-merisation of the acetal protected glycolaldehyde (4) under strongly basic conditions furnished, after deacetalization, DL-threose (ca.10%) and a 2:1 mixture of DL-allose and -mannose (ca.), 20% respectively.

In a preparation of L-lyxose (8) from L-arabinitol (Scheme 3), oxidation of the free primary hydroxyl group of intermediate (5) was achieved by photolysis of the azide (6) to give the imine (7), and subsequent hydrolysis.” A rapid, stereoselective synthesis of D-mannose from D-arabinose 2,3:4,5-diacetonide is shown in Scheme 4; both reaction steps took only minutes and isolation of the intermediate (9) was not necessary. The procedure has been used for “C-labelling. The key-steps in the conversion of D-glucose to L-glucose (Scheme 5) were the introduction of a protected hydroxymethyl branch at C-1 of the hexonolactone derivative (10) and the decarboxylation of the hepturonic acid derivative (11). D-Allose has been obtained from levoglucosenone by stereoselective reduction at C-2 followed by ci’s-hydroxylation of the double bond from the less hindered face and hydrolytic opening of the anhydro-ring.

An efficient preparation of methyl α-L-tagatopyranoside (13) from 1,5-anhydro-D-galactitol (12) in which C-6 of the starting material became C-1 of the product is outlined in Scheme 6. The selectively 1,3,4-protected fructofuranose derivative (15) is readily available by cleavage of the glycosidic bond of the perbenzylated sucrose silyl ether (14) with concomitant loss of the silyl group, by use of HBF4. [4-2H],[6-3H]-labelled glucose is referred to in Pan 5 of this Chapter.

Chain-extended Compounds. – Unusual hexoses and higher carbon sugars have been produced by use of fructose 1,6-diphosphate aldolase which catalysed firstly, in combination with triosephosphate isomerase, the release of dihydroxyacetone phosphate (DHAP) from fructose 1,6-diphosphate and secondly the stereospecific condensation of DHAP with a variety of simple aldehydes. Two examples are given in Scheme 7.

A full paper on the synthesis of octoses by the “naked sugar” approach has been published (see Vol.23, Chapter 2, ref.31). An improved, shorter version of this synthesis employs a Wittig Homer reaction instead of the original Mukayama cross-aldolization for chain-extension. Similar work has been reported by a Japanese group.

The stereochemistry of the addition of organometallics (LiCH2SO 2Ph, MeMgBr) in the presence or absence of added metal salts (ZnCl2, TiCl4, SnCl4, etc.) to compounds (16) and (17) (exemplifying an α-alkoxy- and an α,β-dialkoxy-aldehyde, respectively) has been examined. The product ratios were strongly influenced by the counter cations, in particular by Sn4+ and Zn2+, which enhanced α-chelation and by Mg2+, which favoured β-chelation. Hydroxymethylene-extension of the α-D-manno-dialdehydo sugar (20) with the Grignard reagent (18) represents an improvement over earlier procedures employing (19), in that the addition product (21) is stable, allowing, for example, benzylation and glycosylation prior to the oxidative removal of the silyl group (Scheme 8). The four stereomeric octofuranose derivatives (24) have been produced from the dialdehydo sugars (23), obtained by DIBAL reduction of the protected D-gluco-and L-ido-furanurono-6,3-lactones (22) by treatment with allylmagnesium bromide.

The Wittig adducts (26) of the branched 1,5-dialdehydopentofuranose derivative (25) were reduced to the allylic alcohols (27) which underwent a Claisen rearrangement as shown in Scheme 9 to give, after selective reduction of the ester group and hydrogenation of the double bond, 3,5-dialkylated 3,5,6-trideoxy-heptose derivatives (28).

Chain-extension of aldoses or dialdoses with ethyl diazopyruvate furnished sugar 2,4-diketoesters, such as compounds (29) and (30), respectively, suitable for transformation into complex carbohydrates containing heterocyclic moieties,” and Pd-catalysed trimethylene cycloaddition (see Trost et al., J. Am. Chem. Soc, 1991, 113, 9007) of diacetone D-galacto-dialdose (32) employing the bifunctional reagent (31) represents a useful carbohydrate homologation for ionophore synthesis (Scheme 10). The D-ribo-dialdose derivative (33) reacted with a terpene-derived phosphonium salt to give the precursor (34) of hopane polyols. Monodeoxy-octose, -nonose, and -decose derivatives have been synthesized by cycloaddition of nitrile oxides to sugar alkenes and reductive hydrolysis of the resulting 2-isoxazolines. The method is illustrated in Scheme 11. Chain-extension at the reducing end of unprotected tetroses to hexoses has been effected by reaction with allyl bromide and tin metal under the influence of ultrasound, followed by ozonolysis of the double bond. D-Arabinose, for example, was converted to the unsaturated deoxy derivative (35) and hence to the peracetylated methyl 2-deoxy heptoside (36). An overall yield of 43% indicated good threo selectivity in the C-C bond forming step.” Chain-elongation of D-arabinose at the reducing terminus with Ph3 P=CH-CH=CH-CO2t gave the di-unsaturated product (37) which on catalytic hydrogenation furnished methyl 2,3,4,5-tetradeoxy-D-arabino-nononate.

Treatment of 2,3-O-isopropylidene derivatives of furanoses with Grignard reagents RMgBr (R = Me, Ph, CH2=CH, CH2-CH-CH2) gave consistently main products with erythro configuration across the new double bond, e.g., compound (39) from di-O-isopropylidene-D-mannose (38). Use of the corresponding alkyl lithium reagents, although furnishing mainly the threo product (40) from (38), gave in general erythro/threo mixtures.”

Further examples of four-carbon chain-extensions with 2-(trimethylsilyloxy) furan (see Vol.24, Chapter 2, Scheme 7) have been reported. Application of this method to O-isopropylidene-D-glyceraldehyde afforded D-glycero-D-talo-heptose triacetonide (41), and an iterative procedure gave D-glycero-D-talo-L-talo-undecanose pentaacetonide.” Similarly, a 8-O-benzyl-L-threo-D-talo-octose derivative was obtained from 4-O-benzyl-2,3-O-isopropylidene-L-threose.

Carbohydrate lactones, e.g., compound (42), added TMSCH2Li and TMSCHC2Li to form 1-deoxy- and 1-chloro-1-deoxy-ketose derivatives (43) and (44), respectively, in good yields. Exposure of lactone (42) to the aryllithium reagent (46) gave, after hydrolysis, the spiroketal (45).

Spiroketals have also been produced from 1-exo-methylene compounds derived from aldonolactones: i) by epoxidation, the products hydrolysing and solvolysing to give ketoses and ketosides, respectively, and ii) by iodoallyloxylation to give allyl 1-deoxy-1-iodo-ketosides followed by radical cyclization. Otherwise, they have been made by solvolysis of [4+2]-cycloadducts of 1-C-(3-acetoxypropyl)glycals and bis(trichloroethyl)azodicarboxylate. From the resulting 2-deoxy-2-hydrazonon-4-ulose spiroketals, 2-amino-2-deoxy spiroketals are obtainable.

The synthesis of ketose nucleosides from 1-deoxy-1-nitro-D-ribose is covered in Chapter 20.

A review with 50 refs. on the melting point of sucrose and possible reasons for the discrepancies in the literature has appeared.

In a theoretical study on the glass-transition behaviour of maltose/water mixtures, predicted Tg values were close to those obtained experimentally.

The apparent molal volumes and compressibilities of galactose, glucose, maltose, sucrose, and dextran have been calculated from measurements of the density and ultrasound velocity of their aqueous solutions at 25°C. 13C- and 1H-n.m.r. lattice relaxation times T, have been used to provide information on the temperature dependence of the rotational mobility of both the sugar and the water molecules in concentrated aqueous solutions of sucrose and trehalose.

The kinetics of the liquid-phase heterogeneous isotopic exchange reaction between [1-3H]monosaccharides and molecular hydrogen have been found to depend on the structure of the sugar, the catalyst (PdO/Al2O3 or PdO/BaSO4), and the buffer used. The concentration of the acyclic sugar forms appeared to play a crucial role in determining the kinetic mechanism. The acid-catalysed hydrolysis of sucrose and the oxygen exchange at the anomeric centres of various hexoses, monitored by use of the 18O-isotopic shift in 13C-n.m.r. spectroscopy, have been discussed in a symposium report. Similar work has been reported for D-ribose and its 2-deoxy analogue. The results have been analysed in terms of the hydration kinetics of the open-chain forms. The proton affinities and the deprotonation enthalpies of the primary and anomeric hydroxyl groups of D-gluco- and L-sorbo-pyranose have been calculated, as well as the proton affinities of the ring oxygen atoms of these two hexoses.

The determination of the absolute configuration of monosaccharides by use of asymmetric glycosyl esters is covered in Chapter 7.

4 Isomerization

The steady state kinetics and thermodynamic activation constants of the heptamolybdate ion-catalised glucose-mannose epimerization, a model for metalloenzyme catalysis, have been determined for both directions of the reaction.

A further paper, in Japanese, on the epimerization of aldohexoses catalyzed by complexes of Ni(II) with various N-alkylated ethylene diamines has been published (see Vol.24, Chapter 2, refs.47,48). In the epimerization of D-glucose by optically active Ni(II) N, N- diethylcyclohexane-l,2-diamine, 36:44 and 60:40 glucose/mannose equilibrium mixtures were obtained by use of the (R,R and (S,S)-enantiomer, respectively.

The isomerization of lactose to lactulose by alkaline ion exchangers has been described. The heterogeneous catalyst was found not only to simplify the process but also to enhance the selectivity.

5 Oxidation

The electrochemical oxidation of glucose has been reviewed (49 refs.). Special attention was given to the effect of the electrode material on the process, and to the adsorption of glucose and its oxidation products on the electrode surface. The oxidation of glucose with single-crystal platinum electrodes in different orientations has been studied. Pronounced structural sensitivity of the reaction was discovered, the Pt(111) and its vicinal surfaces being the most active.

In an investigation of the transition metal-catalysed oxidation of sucrose by oxygen, high selectivity for OH-6 and OH-6′ was observed with platinum on carbon at 100°C and neutral pH, with no evidence of reaction at OH-1′.

Papers have been published on the kinetics of oxidation of D-mannose and D-rhamnose by Ce(IV) sulfate, and of D-galactose, L-sorbose, L-arabinose, and D-xylose by OsO4 in alkaline aqueous media. A mechanism involving free radicals has been proposed in the former case, and formation of an activated OsO4 – enediol complex in the latter. A kinetic study of the reactions related to the Mn(II)-catalysed bromate/aldose oscillating system has been reported.

(Continues…)Excerpted from Carbohydrate Chemistry Volume 25 by R. J. Ferrier. Copyright © 1993 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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