Химические картинки, клипарт::Chemfiles ... - 2....

Vol. 1 Carbohydrates 1

Carbohydrates

FRIEDER W. L ICHTENTHALER, Institut fur Organische Chemie, Technische Universitat Darmstadt,

Darmstadt, Federal Republic of Germany

1. Introduction . . . . . . . . . . . . . . . 12. Monosaccharides . . . . . . . . . . . . 22.1. Structure and Configuration . . . . . 22.2. Ring Forms of Sugars: Cyclic

Hemiacetals . . . . . . . . . . . . . . . . 52.3. Conformation of Pyranoses and

Furanoses . . . . . . . . . . . . . . . . . 52.4. Structural Variations of Monosac-

charides . . . . . . . . . . . . . . . . . . 73. Oligosaccharides . . . . . . . . . . . . 83.1. Common Disaccharides. . . . . . . . 83.2. Cyclodextrins . . . . . . . . . . . . . . . 114. Polysaccharides . . . . . . . . . . . . . 115. Nomenclature . . . . . . . . . . . . . . 146. General Reactions. . . . . . . . . . . . 176.1. Hydrolysis . . . . . . . . . . . . . . . . . 176.2. Isomerization . . . . . . . . . . . . . . . 186.3. Decomposition . . . . . . . . . . . . . . 187. Reactions at the Carbonyl Group . 187.1. Glycosides . . . . . . . . . . . . . . . . . 187.2. Thioacetals and Thioglycosides. . . 197.3. Glycosylamines, Hydrazones, and

Osazones. . . . . . . . . . . . . . . . . . 20

7.4. Chain Extension . . . . . . . . . . . . . 217.5. Chain Degradation . . . . . . . . . . . 227.6. Reductions to Alditols . . . . . . . . . 227.7. Oxidation . . . . . . . . . . . . . . . . . 238. Reactions at the Hydroxyl Groups . 248.1. Ethers . . . . . . . . . . . . . . . . . . . 248.2. Esters of Inorganic Acids . . . . . . . 258.3. Esters of Organic Acids . . . . . . . . 268.4. Acylated Glycosyl Halides . . . . . . 268.5. Acetals . . . . . . . . . . . . . . . . . . . 279. Carbohydrates as Organic Raw

Materials . . . . . . . . . . . . . . . . . . 289.1. Microbial Synthesis . . . . . . . . . . . 299.2. Chemical Conversions . . . . . . . . . 309.2.1. Furan Derivatives. . . . . . . . . . . . . 309.2.2. Pyrones and Dihydropyranones. . . . 329.2.3. Sugar-Derived UnsaturatedN-

Heterocycles. . . . . . . . . . . . . . . . 349.2.4. Sugar-Based Surfactants. . . . . . . . 379.2.5. Hydrophilic Monomers of

Polyamides. . . . . . . . . . . . . . . . . 3910. References. . . . . . . . . . . . . . . . . 40

1. Introduction

Terrestrial biomass constitutes a multifacetedconglomeration of low and high molecular massproducts, exemplified by sugars, hydroxy andamino acids, lipids, and biopolymers such ascellulose, hemicelluloses, chitin, starch, ligninand proteins. By far the most abundant groupof these organic products and materials, in factabout two thirds of the annually renewablebiomass, are carbohydrates, i.e., a single classof natural products. As the term ‘carbohydrate’(German‘Kohlenhydrate’; French‘hydrates decarbone’) implies, they were originally consid-ered to consist solely of carbon and water ina 1:1 ratio, in recognition of the fact that theempirical composition of monosaccharides canbe expressed as Cn(H2O)n. Today, however, theterm is used generically in a much wider sense,not only comprising polysaccharides, oligosac-charides, and monosaccharides, but substances

derived thereof by reduction of the carbonylgroup (alditols), by oxidation of one or moreterminal groups to carboxylic acids, or by re-placement of one or more hydroxyl group(s)by a hydrogen atom, an amino group, a thiolgroup, or similar heteroatomic groups. A simi-larly broad meaning applies to the word ‘sugar’,which is often used as a synonym for ‘monosac-charide’, but may also be applied to simplecompounds containing more than one monosac-charide unit. Indeed, in everyday usage ‘sugar’signifies table sugar, which is sucrose (Ger-man ‘Saccharose’; French ‘sucrose’ or ‘sac-charose’), a disaccharide composed of the twomonosaccharidesD-glucose andD-fructose.

Carbohydrates appear at an early stage inthe conversion of carbon dioxide into organiccompounds by plants, which build up carbohy-drates from carbon dioxide and water by photo-synthesis. Animals have no way of synthesizing

2 Carbohydrates Vol. 1

carbohydrates from carbon dioxide and rely onplants for their supply. The carbohydrates arethen converted into other organic materials by avariety of biosynthetic pathways.

Carbohydrates serve as sources (sugars) andstores of energy (starch and glycogen); theyalso form a major portion of the supporting tis-sue of plants (cellulose) and of some animals(chitin in crustacea and insects); they play a ba-sic role as part of the nucleic acids DNA andRNA. Other carbohydrates are found as com-ponents of a variety of natural products, suchas antibiotics, bacterial cell walls, blood groupsubstances, glycolipids, and glycoproteins, thelatter, due to their multifaceted carbohydrate-based recognition phenomena, forming the ba-sis of glycobiology.

In the last decade, a large collection ofbooks on carbohydrate chemistry and biochem-istry have appeared, ranging from compara-tively brief introductions [1–3] to more elabo-rate monographs [4–7] and multivolume com-prehensive treatises [8], [9]. They are recom-mended as more profound sources of informa-tion.

2. Monosaccharides

The generic term ‘monosaccharide’ denotes asingle sugar unit without glycosidic connectionto other such units. Chemically, monosaccha-rides are either polyhydroxyaldehydes oral-doses(e.g., glucose) or polyhydroxyketones orketoses(e.g., fructose), the ending ‘ose’ be-ing the suffix to denote a sugar. Monosac-charides are classified according to the num-ber of carbon atoms they contain, i.e., hex-oses and ketohexoses (or hexuloses) of thegeneral formula C6H12O6 or pentoses andpentuloses (C5H10O5). Subdivisions are madeaccording to functional groups which mayalso be present, for example, aminohexoses(C6H13O5N), deoxyhexoses (C6H12O5), andhexuronic acids (C6H10O7). Monosaccharideswith fewer (trioses, tetroses) or more carbonatoms (heptoses, octoses, etc.) are rare.

D-Glucose (→Glucose and Glucose-Containing Syrups, Chap. 2.) [50-99-7], alsoknown as dextrose, blood sugar, or grape sugar(‘Traubenzucker’ in German), is a pentahydrox-yhexanal, hence belonging to the class of aldo-

hexoses (see Section 2.1). Glucose can be con-sidered the parent compound of the monosac-charide family, because it is not only the mostabundant monosaccharide in nature but alsothe one most extensively studied. It occursas such in many fruits and plants, in concen-trations of 0.08 – 0.1 % in human blood, andconstitutes the basic building unit of starch,cellulose, and glycogen. Other ubiquitous al-dohexoses areD-mannose[3458-28-4], occur-ring naturally mainly in polysaccharides (‘man-nans’, e.g., from ivory nut) andD-galactose[59-23-4], a frequent constituent of oligosac-charides, notably lactose and raffinose, andof primary cell wall polysaccharides (pectins,galactans, arabinogalactans). A correspondingisomeric 2-ketohexose isD-fructose[57-48-7](→Fructose), the sweetest natural sugar, whichoccurs in many fruits and in honey, and, glyco-sidically linked, in sucrose and the polysaccha-ride inulin, a reserve carbohydrate for manyplants (chicory, Jerusalem artichoke). Otherimportant natural sugars are the aldopentoseD-ribose [50-69-1], which constitutes a build-ing block of the ribonucleic acids,L-arabinose,widely distributed in bacterial polysaccha-rides, gums and pectic materials, andD-xylose[58-86-6], of widespread occurrence in pen-tosans (‘xylans’) that accumulate as agriculturalwastes (cottonseed hulls, corn cobs).

2.1. Structure and Configuration

D-Glucose, the most abundant monosaccha-ride, has the molecular formula C6H12O6 asshown by elemental analysis and molecularmass determination. As evidenced from ensu-ing reactions (see below) this is consistent witha six-carbon, straight-chain pentahydroxyalde-hyde of the following structural formula, an al-dohexose in carbohydrate notation (Fig. 1).

Figure 1. Structural formula of aldohexoses, of which dueto the four chiral centers (marked by∗) 16 stereoisomersare possible


This structure contains four asymmetric cen-ters, thus 24 = 16 stereoisomers exist, whichcan be grouped into eight pairs of enan-tiomers, and classified asD- and L-sugars.In the D-sugars, the highest numbered asym-metric hydroxyl group (C-5 in glucose) hasthe same configuration as the asymmetric cen-ter in D-glyceraldehyde and, likewise, allL-sugars are configurationally derived fromL-glyceraldehyde. A convenient way to show con-figurational relationships was introduced byEMIL FISCHER in 1891 [10], [11], now termedFischer projection formula (Fig. 2), as it – lit-erally – projects tetrahedral space relationshipsinto a plane. The resulting formulas are sim-ple to write and easy to visualize, yet they re-quire the setting up of conventions: The carbonchain of a sugar is oriented vertically and to therear with the aldehyde group at the top; hydro-gen atoms and hydroxyl groups at the asymmet-ric carbon atoms stand out in front. The result-ing three-dimensional model is then imaginedto be flattened and the groups are laid on theplane of the paper. If the lower-most asymmet-ric center (C-5 in glucose) has the OH groupto the right, it is considered to have theD-configuration. FISCHER’s decision to place theOH group of natural glucose to the right, henceD-glucose, was purely arbitrary, yet proved tobe a fortunate one, since much later, in 1951, itwas proven by special X-ray structural analysis[12] that he had made the right choice.

Figure 2. Configurational representations of the linear(acyclic) form ofD-glucose: Traditional Fischer projectionformula (top left) and its transformation into the more re-alistic dashed-wedged line depictions with the six-carbonchain in zigzag arrangement.

The D-aldose family tree is shown in Fig-ure 3, comprising five of the most importantmonosaccharides, the aldopentosesD-riboseand D-xylose, and the hexosesD-glucose,D-mannose, andD-galactose, each having the hy-droxyl group at the highest-numbered stereo-center (at the bottom) pointing to the right.Likewise, all L-aldoses are configurationallyderived fromL-glyceraldehyde, entailing a fam-ily tree with the lowest OH group to the left;the respective projection formulas being, inessence, mirror images to those in Figure 3.

A similar system is used to build up the se-ries of ketohexoses or hexuloses, i.e., monosac-charides with a keto group at C-2, which there-fore contain one asymmetric carbon atom less(Fig. 4).


Figure 3. TheD-aldose family tree (up to aldohexoses) in their acyclic forms: Common names and Fischer projection formu-las, with secondary hydrogen atoms omitted for clarity.

Figure 4. The D-ketohexose (orD-hexulose) family tree:Trivial names, systematic designation (in brackets) and Fis-cher projection formulas.†Not regarded as being a sugar, due to absence of an asym-metric carbon atom.


2.2. Ring Forms of Sugars: CyclicHemiacetals

In the solid state and in solution monosaccha-rides exist in a cyclic hemiacetal form, ringclosure corresponding to reaction between thealdehyde group and either the C-4-OH or C-5-OH. Cyclization involvingO-4 results in a five-membered ring structurally related to furan andtherefore designated as afuranose, whilst hemi-acetal formation withO-5 gives rise to an es-sentially strain-free, hence sterically more fa-vored, six-membered ring, a derivative of pyran,hence termed apyranose. Either ring forma-tion generates a new asymmetric carbon atomat C-1, the anomeric center, thereby giving riseto diastereomeric hemiacetals which are calledand labeledα andβ. For visualization of thecyclic hemiacetal forms of sugars, HAWORTH,in 1928 [13], introduced his projection formula,in which the rings are derived from the open-chain form and drawn as lying perpendicular tothe paper with the ring oxygen away from theviewer. To facilitate this mode of viewing, thefront part is usually accentuated by wedges asshown in Figure 5 for theβ-anomers of pyra-nose and furanose forms ofD-glucose. The pro-jections devised by MILLS in 1954 [14], corre-sponding to those customary for terpenes andsteroids, are also very useful for revealing thestereochemistry of sugars in their cyclic hemi-acetal forms: the ring is placed in the plane ofthe paper with solid or broken wedge-shapedlines to show the orientation of substituents, i.e.,OH and CH2OH groups.

Figure 5. Haworth and Mills projection formulas for theβ-anomers ofD-glucopyranose andD-glucofuranose (in theformula at the center and at the bottom, the carbon and C-hydrogen atoms are omitted for clarity).

2.3. Conformation of Pyranoses andFuranoses

The concepts of conformation are fundamen-tal to a proper understanding of the structure-property relationships of carbohydrates, mostnotably of the regio- and stereoselectivities oftheir reactions. The conformational analysis ofmonosaccharides is based on the assumptionthat the geometry of the pyranose ring is es-sentially the same as that of cyclohexane and,analogously, that of furanoses the same as thatof cyclopentane – a realistic view, since a ringoxygen causes only a slight change in moleculargeometry. Hence, the rhombus-shaped Haworthformulas which imply a planar ring, and theequally flat dashed-wedged line configurationaldepictions by Mills (Fig. 5) are inadequate torepresent the actual three-dimensional shape ofthe rings and the steric orientation of the ringsubstituents (OH and CH2OH groups). For thesix-membered pyranose ring a number of rec-ognized conformers exist [15]: two chairs (1C4,4C1), six boats (e.g.,1,4B andB1,4 in Fig. 6), sixskews and twelve half-chairs (e.g.,oS2 and5H4

forms).


Figure 6. Conformational forms of pyranose rings: chair(C), boat (B), skew (S) and half-chair (H).To designate each form, the ring atom numeral lying abovethe plane of reference appears as a superscript precedingthe letter, those below the plane are written as subscriptsand follow the letter.

Although there are exceptions, most al-dohexoses adopt the chair conformation thatplaces the bulky hydroxymethyl group at theC-5 terminus in the equatorial position. Hence,β-D-hexopyranosides are predominantly in the4C1 chair conformation, since each of the al-ternative forms outlined in Figure 6, most no-tably the 1C4 chair, are energetically less fa-vored. For glucose, this preference means that,in theα-form, four of the five substituents areequatorial, and one is forced to lie axial; in theβ-form, all substituents are equatorial (Fig. 7).This situation is unique for glucose; the othersevenD-aldohexoses contain one or more axialsubstituents.

Figure 7. Cyclic hemiacetal forms ofD-glucose in con-figurational representation. In solution, these forms rapidlyinterconvert through the energetically unfavorable acyclicform; in water at 25◦C the two pyranoid forms are nearlyexclusively adopted, the equilibrium mixture amounting to62 % of theβ-p and 38 % of theα-p anomers. From water,D-glucose crystallizes in theα-pyranose form.The six-membered (pyranose) ring is denoted by the sym-bol p after the three-letter symbol for the monosaccharide(for example, Glcp), the five-membered (furanose) ringcorrespondingly is signated by anf (e.g., Glcf ).

The hexulose counterpart to the con-formational forms of D-glucose is theD-fructose isomerization scheme depicted in Fig-ure 8. Whilst the crystalline product is theβ-D-fructopyranose in the2C5 chair conformationas evidenced by X-ray analysis [16], on dissolu-tion in water, equilibration is essentially instan-taneous to yield a mixture mainly containing theβ-p-form (73 % at 25◦C, the only sweet one infact), together with theβ-f - (20 %),α-f - (5 %)and α-p-forms (2 %) [17]. The acyclic formthrough which equilibration occurs is present toa minute extent only.


Figure 8. Forms ofD-fructose in solution. In water, themajor conformers are theβ-pyranose (β-p, 73 % at 25◦C)andβ-furanose (β-f , 20 %) forms [17]. On crystallizationfrom water,D-fructose adopts the2C5 chair conformationin the crystal lattice as evidenced by X-ray analysis [16].

The principal conformations of the furanosering are theenvelope(E) – one atom lying aboveor below a plane formed by the other four ringatoms – or thetwist (T) arrangement, in whichthree ring atoms are in a plane and the othertwo above and below, respectively. As energydifferences between the variousE and T con-formations are small, the form actually adopteddepends on the type of ring substitution (hex-oses, hexuloses, pentoses), their configuration,their solvation and the type of intra- or inter-molecular hydrogen bonding present. Accord-ingly, the exact conformation of an individualfuranose is usually not known – except for thecrystalline state when an X-ray structural anal-ysis is available. Thus, the planar Haworth andMills projection formulas are the preferred wayof drawing furanose forms (Fig. 9).

Figure 9. The envelope conformation (top left) is the3Eform as defined by the C-3 atom lying above the planeformed by the other ring atoms. The defined plane for thetwist form (top right) is the triangle given by C-1, C-4,and O-4, entailing the conformational description3T2. Inaprotic solvents (dimethylsulfoxide)D-fructose populatestheE2 envelope conformation to a substantial extent [17],whilst in crystalline sucrose, theβ-D-fructofuranose por-tion adopts the4T3 twist form [18], [19] (bottom entries).

2.4. Structural Variations ofMonosaccharides

Sugars may possess functionalities other thanhydroxyl groups. Amino sugars are aldoses,which have a hydroxyl group replaced by anamino functionality, e.g.,D-glucosamine(2-amino-2-deoxy-D-glucose), which is one of themost abundant. In itsN-acetylated form (N-acetyl-D-glucosamine), it is a constituent ofthe polysaccharide chitin (→Chitin and Chi-tosan), that forms the hard shells of crus-taceans and other anthropods, but also ap-pears in mammalian glycoproteins and linksthe sugar chain to the protein. Monosaccharideslacking a hydroxyl group at the terminal C-6,i.e., 6-deoxy-sugars, are likewise of wide oc-currence, for example,L-rhamnose(6-deoxy-D-mannose) is found in plant and bacterialpolysaccharides whereasL-fucose(6-deoxy-D-galactose) is present in combined form in ani-mals, plants, and microorganisms. 2-Deoxy-D-erythro-pentose (2-deoxy-D-ribose) is the ex-ceedingly important sugar component of DNA,various mono-, di- and trideoxy sugars are con-stituents of many antibiotics, bacterial polysac-charides, and cardiac glycosides.


The uronic acids are aldoses that containa carboxylic acid chain terminating function,and occur in nature as important constituents ofmany polysaccharides. TheD-gluco compound,D-glucuronic acid, was first isolated from urine(hence the name), in which it occurs as gly-cosides and glycosyl esters of toxic substancesthat the body detoxifies in this way.

N-Acetyl-D-glucosamine 2-Deoxy-D-ribose2-acetamido-2-deoxy-D-glucopyranose(D-GlcNAcp)

2-deoxy-D-erythro-pentafuranose(D-dRibf )

L-Fucose L-Rhamnose6-deoxy-L-galactopyranose 6-deoxy-L-mannopyranose(L-Fucp) (L-Rhap)

D-Glucuronic acid D-Apiose(D-GlcAp) 3-C-hydroxymethyl-D-glycero-

tetrose(D-Apif )

Branched-chain sugars, i.e., saccharides witha non-linear carbon chain, are comparativelyuncommon, the more widely occurring beingD-apiose(3-C-hydroxymethyl-D-glycero-tetrose),richly present in polysaccharides of parsleyand duckweed [20], andD-hamamelose(2-C-hydroxymethyl-D-ribose), a component of thebark of witchhazel [21].

3. Oligosaccharides

Oligosaccharides are compounds in whichmonosaccharide units are joined by glycosidiclinkages, i.e., simple polymers containing be-tween two and ten monosaccharide residues.Accordingly, there are disaccharides – a dis-accharide composed of two hexopyranoses canhave 5120 distinguishable isomeric forms –trisaccharides, tetrasaccharides, etc. They maybe further subdivided into homo- (consist-

ing of only one type of sugar) and hetero-oligosaccharides, and into those that are reduc-ing (presence of a free hemiacetal group) ornon-reducing. A comprehensive listing of thedi-, tri-, and higher oligosaccharides known by1990 is available [22].

3.1. Common Disaccharides

Sucrose,affectionately called “the royal car-bohydrate” [23], is a non-reducing disaccharidebecause its component sugars,D-glucose andD-fructose, are glycosidically linked throughtheir anomeric carbon atoms: Sucrose is aβ-D-fructofuranosylα-D-glucopyranoside (seeFig. 10). It is widely distributed throughout theplant kingdom, is the main carbohydrate reserveand energy source and an indispensable di-etary material for humans (→Sugar). For cen-turies, sucrose has been the world’s most plenti-ful produced organic compound of low molec-ular mass, the present annual production fromsugar-cane and sugar beet being an impressive130×106 t [24].

α,α-Trehalose,a non-reducingD-glucosylD-glucoside occurs extensively in the lowerspecies of the plant kingdom (fungi, youngmushrooms, yeasts, lichens, and algae). Inbaker’s yeast it accounts for as much as 15 % ofthe dry mass, in the metabolic cycle of insects itcirculates like glucose does in the mammaliancycle. Similarly nonreducing, due to being agalactosylated sucrose, is the trisaccharideraf-finose, distributed almost as widely in the plantkingdom as sucrose, yet in lower concentration(e.g., less than 0.05 % in sugar beets).


Figure 10.Common structural representations of sucrose (top entries), the molecular geometry realized in the crystal featur-ing two intramolecular hydrogen bonds between the glucose and fructose portion [18], [19] (bottom left), and the stericallysimilar disposition of the two sugar units towards each other in aqueous solution form, caused by hydrogen bonding througha ‘water bridge’ [25]. The bottom entries show the solvent-accessible surfaces (dotted areas) of the crystal form (left) and theform adopted in water [25] (right), clearly demonstrating that sucrose has an unusually compact overall shape, more so thanany other disaccharide.

α,α-Trehalose [99-20-7] Raffinose [512-69-6]α-D-Glucopyranosylα-D-glucopyranoside

α-D-Galactopyranosyl-(1→6)-sucrose

(α-D-Glcp[1↔1]α-D-Glcp) (α-D-Galp-(1→6)-α-D-Glcp(1↔2)-β-D-Fruf )

There are only very few naturally occurringoligosaccharides with a free anomeric hydroxylgroup, which therefore possess reducing prop-erties. The most important example islactose(milk sugar,→Lactose and Derivatives), an in-gredient of the milk of mammals (up to 5 %in cows). As it is produced on an industrialscale from whey, it represents the only large-scale available sugar derived from animal ratherthan plant sources. Uses include human food,pharmaceuticals, and animal feeds. The reduc-


ing gluco-disaccharidescellobioseandmaltose(malt sugar) are chemical or enzymatic hydrol-ysis products of the polysaccharides celluloseand starch, respectively, and, hence are not re-garded as native oligosaccharides.

Lactose[63-42-3]β-D-Galactopyranosyl-(1→4)-D-glucopyranose(β-D-Galp-[1→4]-D-Glcp)

Cellobiose[528-50-7]β-D-Glucopyranosyl-(1→4)-D-glucopyranose(β-D-Glcp-(1→4)-D-Glcp)

Maltose [69-79-4]α-D-Glucopyranosyl-(1→4)-D-glucopyranose(α-D-Glcp-(1→4)-D-Glcp)

Isomaltulose(palatinose,→Sugar Alco-hols, Chap. 5.1.) andlactulose, both pro-duced in fairly large amounts from su-crose and lactose, respectively, are 6-O-glucosyl- and 4-O-galactosyl-fructoses. The su-crose→ isomaltulose transformation, industri-ally realized at a 40 000 t/a-scale [26], is ef-fected by aProtaminobacter rubrum-inducedglucosyl shift from the anomeric fructosyl oxy-gen to its O-6, taking place in mostly in-tramolecular fashion via a closed-shell inter-mediate [27], whilst the generation of lactu-lose from lactose, presently running at a 12 000t/a level, comprises a base-promoted C-1→C-2 carbonyl shift. Most of the isomaltulose pro-duced is subsequently hydrogenated to isomalt(→Sugar Alcohols, Chap. 5.2.), a low-calorie

sweetener with the same taste profile as su-crose, lactulose (→Lactose and Derivatives,Chap. 2.1.) has medical and pharmaceutical ap-plications, mainly for treating intestinal disor-ders.

Isomaltulose[13718-94-0]α-D-Glucopyranosyl-(1→6)-D-fructofuranose(α-D-Glcp-(1→6)-D-Fruf )

Lactulose[4618-18-2]β-D-Galactopyranosyl-(1→4)-D-fructopyranose(D-Galp-β(1→4)-D-Fruf )

Other Heterooligosaccharides.Het-erooligosaccharides of considerably highercomplexity occur in large variety in plants, ani-mals and microorganisms where they are cova-lently bound to proteins (‘glycoproteins’) andlipids (‘glycolipids’) or other hydrophobic enti-ties, and, as such, are implemented in a range ofkey biological processes: cell-cell recognition,fertilization, embryogenesis, neuronal develop-ment, hormone activities, the proliferation ofcells and their organization into specific tis-sues, viral and bacterial infection and tumorcell metastasis [28–30]. Red blood cells, forexample, carry carbohydrate antigens whichdetermine blood group types in humans: typeA people have the tetrasaccharide in Figure 11with R = NHAc (i.e., a GalNAc residue) as akey antigen linked by lipid components to thesurfaces of red blood cells; in type B blood, thetetrasaccharide determinant is exceedingly sim-ilar – formal replacement of NHAc by OH, i.e.,


GalNAc by Gal – yet on mixing with type Ablood leads to clumping and precipitation [31].

Figure 11. Human blood groups determinants: Differ-entiation between type A (R = NHAc) and B (R = OH) iseffected by relatively simple changes within a branchedtetrasaccharide linked to lipid components on the surfaceof red blood cells.

All N-glycoproteins (N-glycans) share thepeptide-linked pentasaccharide fragment inFigure 12, consisting of three mannose unitsin a branched arrangement and two GlcNAcresidues, of which the terminal one isN-glycosidically linked to an asparagine moietyof the protein. Branching out from this uniformcore region are monosaccharides and oligosac-charide chains of high structural diversity lead-ing to multiple types of branched and un-branched glycoproteins [32].

3.2. Cyclodextrins(→Cyclodextrins)

Although discovered more than 100 years ago,the cyclic glucooligosaccharides termed cy-clodextrins (based on dextrose, which is an oldname for glucose) remained laboratory curiosi-ties until the 1970s when they started to beused commercially [33]. Their large-scale pro-duction is based upon the degradation of starchby enzymes elaborated byBacillus macerans(‘CGTases’), involving excision and reconnec-tion of single turns from the helicalα-(1→4)-glucan (amylose) chain (cf. Fig. 13) to pro-vide cyclic α-(1→4)-linked glucooligosaccha-rides with six, seven and eight glucose units.

They are namedα-, β- andγ-cyclodextrin, re-spectively.

Cyclodextrins are truncated cones with well-defined cavities. All secondary hydroxyl groupsare located at the wider rim of the cone leavingthe primary CH2OH groups to protrude fromthe narrower opening. The respective cavities,as exemplified by that ofα-cyclodextrin with itssix glucose units (Fig. 14, [34], [35]), are dis-tinctly hydrophobic in character, and show anamazing propensity to form stable complexeswith a large variety of equally hydrophobic,sterically fitting guest molecules by incorporat-ing them into their cavities [33], [34], chang-ing the physical and chemical properties of theincluded guest. The features and properties ofthe resulting cyclodextrin inclusion compoundshas led to the exploitation of cyclodextrins for awide variety of purposes: as drug carriers [36],[37], as stationary phases for the separation ofenantiomers [38], [39], as building blocks forsupramolecular structures [40], and as enzymemodels [41].

4. Polysaccharides

The bulk of the annually renewablecarbohydrate-biomass are polysaccharides (gly-cans), such as cellulose, hemicelluloses, chitin,starch, and inulin. Invariably composed ofmonosaccharide units, they have high molec-ular masses and, hence, differ significantlyin their physical properties. The majority ofnaturally occurring polysaccharides contain80 – 100 units, with a few though made up ofconsiderably more.

Cellulose (→Cellulose) [9004-34-6] is anunbranched glucan composed ofβ-(1→4)-linked D-glucopyranosyl units (see Fig. 15)with an average molecular mass equivalent toabout 5000 units. It is the most abundant or-ganic material found in the plant kingdom,forming the principal constituent of the cellwalls of higher plants and providing them withtheir structural strength. Cotton wool is al-most pure cellulose, but in wood, the otherchief source of the polymer, cellulose is foundin close association with other polysaccha-rides (mainly hemicelluloses) and lignin. X-ray analysis and electron microscopy indicate


Figure 12. Central core region common to allN-glycoproteins is a pentasaccharide,N-glycosidically linked to the carbamidonitrogen of an asparagine moiety (Asn) within the peptide chain

Figure 13. Sketch representation of a left-handed, single-stranded helix of VH-amylose (top), and ofα-cyclodextrin (bot-tom), which de facto represents a single turn of the amylose helix excised and re-connected byBacillus macerans-derivedenzymes (CGTases). The close analogy allows to consider VH-amylose as a tubular analog ofα-cyclodextrin.


Figure 14. Top: Ball-and-stick model representations of the X-ray-derived solid-state structure ofα-cyclodextrin, togetherwith its solvent-accessible surface, shown as a dotted pattern.Bottom: Cross section contour of a plane perpendicular to the macrocycle’s mean plane with approximate molecular dimen-sions [34], [35].

that these long chains lie side by side in bun-dles, held together by a multiplicity of hydro-gen bonds between the numerous neighboringOH groups. These bundles are twisted togetherto form rope-like structures, which themselvesare grouped to form the fibers that can be seen.In wood (→Wood, Chap. 1.) these cellulose“ropes” are embedded in lignin to give a struc-ture that has been likened to reinforced con-crete.

Chitin (→Chitin and Chitosan) is apolysaccharide composed ofβ-(1→4)-linked 2-acetamido-2-deoxy-D-glucopyranosyl residues(cf. Fig. 15), of which about one out of everysix is not acetylated. Chitin is the major or-ganic component of the exoskeleton (shells)of insects, crabs, lobsters, etc. and, hence, anabundant byproduct of the fishing industries.

Chitosan, a related water-soluble polysaccha-ride in which the vast majority of residues isnot acetylated (i.e., aβ-(1→4)-linked chain of2-amino-2-deoxy-D-glucose residues), can beobtained from chitin by deacetylation in con-centrated sodium hydroxide solution.

Starches (→Starch). The principal food-reserve polysaccharides in the plant kingdomare starches. They form the major source of car-bohydrates in the human diet and are thereforeof great economic importance, being isolated onan industrial scale from many sources. The twocomponents, amylose and amylopectin, vary inrelative amount among the different sourcesfrom less than 2 % of amylose in waxy maizeto about 80 % of amylose in amylomaize (bothcorn starches), but the majority of starches con-tain between 15 and 35 % amylose.


Figure 15.Structural representations of segments of cellulose (R = OH), chitin (R = NHAc), and chitosan (R = NH2).

Amylose[9005-82-7] is made up of longchains, each containing 100 or moreα-(1→4)-linked glucopyranosyl units which due to thekink in everyα-glycosidic linkage tend to coilto helical segments with six glucose units form-ing one turn (see sketch in Fig. 13). Amyloseis the fraction of starch that gives the intenseblue color with iodine, which has its cause inthe trapping of iodine molecules within the hy-drophobic channel of the helical segments ofthe polysaccharide (Fig. 16).

Amylopectin[9037-22-3] is also an α-(1→4)-glucan, yet there is a branch point viaO-6 about every 25 units. The molecular sizeof amylopectin is of the order of 106 D-glucoseresidues, making it one of the largest naturallyoccuring molecules. The secondary structure ischaracterized by a several hundred linear chainsof about 20 – 25 glucose units each, which areconnected in a variety of arrangements to giveclusters for which the tassel-on-a-string model(see Fig. 17) has been proposed. With iodine,amylopectin produces only a dull-red color, in-dicating that the short linear chain portions can-not coil effectively to the helices required forformation of inclusion complexes.

Dextrans (→Dextran) are linear water-solubleα-(1→6)-glucans with only occasionalbranches viaO-2, O-3 or O-4. They are gener-ated from sucrose by a large number of organ-isms, of whichLeuconostoc mesenteroidesisused to produce the slightly branched commer-cial dextran, used clinically as a plasma volumeexpander.

Inulin is a polysaccharide composed ofβ(1→2)-linked D-fructofuranose units withvarying chain length of about 15 – 30 units. Itis present to the extent of 30 % or more in vari-ous plants such as dahlia or Jerusalem artichokewhere it replaces starch either partially or com-pletely as the food storage carbohydrate [44],[45]. The structure of inulin is unique in leav-ing no ‘reducing end’, as this is glycosidically

blocked by anα-D-glucopyranose residue – asucrose unit in fact (Fig. 18).

Figure 18. Nystose fragment of inulin, showing sub-fragments corresponding to sucrose, inulobiose and 1-kestose. Commercial inulins, e.g., those isolated fromchicory, have a degree of polymerization far below thatfound in other polysaccharides, their molecular sizes rang-ing from around 5 to 30 units [43].

Other Polysaccharides(→Polysaccharides).A plethora of other homo- and heteropolysac-charides are abound in nature, most notablyD-xylans(hemicelluloses with linear chains ofβ-(1→4)-D-xylopyranosyl units),pectins(princi-pal constituentD-galacturonic acid), plant gums(building blocks D-galactose,L-arabinose,L-rhamnose) and various algal and microbialpolysaccharides with, in part, unusual sugarunits: L-guluronic andD-mannuronic acids inalginates, glucuronic acid and pyruvate ac-etals in agar, sulfated galactosyl residues incarrageenans, or ribitol phosphates inteichoicacids. Excellent accounts on this subject havebeen given [46], [47].

5. Nomenclature

According to common practice, trivial namesare used for monosaccharides and for many nat-


Figure 16. Sketch illustration of a left-handed, single stranded helix of VH-amylose (top) and more detailed representationof its molecular geometry based on X-ray diffraction data [42] and calculation of the solvent-accessible contact surfaces [43],indicated by dots with ball-and-stick models superimposed.Center: The channel generated by the helical arrangement of theα-D-glucose residues, of dimensions corresponding to thoseof the cavity ofα-cyclodextrin, is clearly apparent. The outside surface area of VH-type amylose is uniformly hydrophilic (inconformity with its solubility in water) whereas the center channel is as distinctly hydrophobic – predestined to incorporateequally hydrophobic guests such as iodine or fatty acids [43].Bottom: A linear polyiodide chain embedded into the channel, corresponding to the intense blue starch-iodine complex [43].

urally occurring oligosaccharides. With the de-velopment of carbohydrate chemistry, however,and ever-increasing numbers of newly definedcompounds, it has become necessary to intro-duce a semisystematic nomenclature which hasbeen approved by the joint commission of IU-PAC (International Union of Pure and AppliedChemistry) and IUB (International Union ofBiochemistry) [48]. This nomenclature is basedon the classical names for monosaccharideswhich appear, written in italics, as a “configura-

tional prefix”. For example,D-xylo, L-arabino,D-gluco refer to the distribution of asymmet-ric carbon atoms along a carbon chain of anylength, designating the configuration of the cor-responding monosaccharide.

Monosaccharides with an aldehydic car-bonyl or potential aldehydic carbonyl group arecalled aldoses; those with a ketonic or potentialketonic carbonyl group, ketoses, with the chainlength given by the root, such as pentose, hex-ose, or heptose and pentulose, hexulose, etc. In


Figure 17. Schematic representation of a section of amylopectin with anα(1→6)-branch of a helical chain ofα(1→4)-glucopyranosyl residues (left), with the tassel-on-string model of its higher level structure (φ= reducing end)

ketoses the position of the keto group is indi-cated by the position number.D-Fructose is sys-tematically namedD-arabino-2-hexulose.

Replacement of a hydroxyl group by hy-drogen is indicated by the prefix deoxy,e.g., L-rhamnose is a 6-deoxy-L-aldohexoseof manno-configuration. Replacement of a hy-droxyl group by any other substituent is for-mally regarded as going via the deoxysugar.Thus a sugar with an amino group instead ofOH is called an amino-deoxysugar. Formationof ether groups, most commonly methyl, is in-dicated by adding ‘O-methyl-’ to the front ofthe name preceded by the number of the car-bon atom whose hydroxyl group has been ether-ified. Esters, for example, acetates are shownby adding either ‘O-acetyl-’ before the name or‘acetate’ after it, in each case again preceding itwith the appropriate carbon number.

The ring size is indicated by a suffix: pyra-nose for six-membered rings, furanose forfive-membered rings, and pyranulose for six-membered ketose rings. The six-memberedcyclic hemiacetal ofD-fructose is namedD-arabino-2-hexopyranulose. The symbolα or βfor the anomeric configuration is always writtentogether with the configurational symbolD or L

(α-D, β-D, α-L, β-L).Names of oligosaccharides are formed by

combining the monosaccharide names, usu-ally the trivial names. The nonreducing dis-

accharide sucrose isβ-D-fructofuranosylα-D-glucopyranoside. The endings “yl” and “ide”describe the fructose part as the aglycone andthe glucose part as the glycone in this “glyco-side”. It is thus clearly indicated that both sug-ars are glycosidically linked by their anomerichydroxyl groups. In reducing oligosaccharidesthe reducing monosaccharide is the root, andall attached monosaccharide units are namedas substituents. The disaccharide lactose istherefore namedβ-D-galactopyranosyl-(1→4)-D-glucopyranose. Position numbers and arrowsindicate aβ-configurated glycosidic bond be-tween the anomeric hydroxyl group (carbonatom 1) ofD-galactose (glyconic part) and thehydroxyl group at carbon atom 4 ofD-glucose(aglyconic part).

For description of more complex oligosac-charides an abbreviation system has come intouse - as for oligopeptides and oligonucleotides- that is unambiguous and practical: eachmonosaccharide is abbreviated by a three-lettersymbol, comprising the first three letters of itstrivial name, i.e.:

Glucose Glc Xylose XylFructose Fru Arabinose AraGalactose Gal Ribose RibMannose Man Deoxyribose dRibFucose Fuc Glucosamine GlcNRhamnose Rha N-Acetylglucosamine GlcNAc


The anomeric configuration andD- or L-affiliation is written before the three-letteracronym, the ring size (p for pyranose,f forfuranose) is added to the end, followed by theintersaccharidic linkage position in the caseof oligosaccharides. Sucrose (Fig. 10), accord-ingly, is β-D-Fruf -(2→1)-α-D-Glcp, lactoseβ-D-Galp-(1→4)-D-Glcp.

6. General Reactions

6.1. Hydrolysis

The hydrolysis of disaccharides such as su-crose and lactose, or polysaccharides like starchand cellulosic materials to their free componentsugars is of great importance in the food andfermentation industries. It can be effected byenzymes called glycosidases or by acid treat-ment.

Enzymatic hydrolysis proceeds with highspecificity towards both the sugar and the con-figuration at the anomeric center. Maltase, anα-D-glucosidase obtainable from barley malt,catalyses the hydrolysis ofα-linked di-, oligo-and polysaccharides (sucrose, maltose, starch,dextrans), whereas the almond emulsin-derivedenzyme is aβ-glucosidase cleaving onlyβ-linked glycosides.

Acid-induced hydrolysis of glycosides re-quires comparatively harsh conditions, stan-dards being 1 M sulfuric acid at 100◦C for4 h for hexose-containing polysaccharides and0.25 M H2SO4 at 70◦C for pentosans. Par-tial degradation of the resulting monosaccha-rides can usually not be avoided whatever con-ditions are used [49], [50]. Thus, aside fromenzymatic hydrolysis, acid hydrolysis ofstarchis industrially performed on a 106 t/a basis,the resultingD-glucose being used in liquidform (corn syrup) as a sweetener (→Glucose-and Glucose-Containing Syrups, Chap. 4.). An-other significant industrial product, in fact theonly large-volume organic chemical preparedfrom carbohydrate sources (∼200 000 t/a), isfurfural (2-furaldehyde) [51], [52]. The tech-nical process involves exposure of agricul-tural or forestry wastes to aqueous acid andfairly high temperatures, thepentosansfirstbeing hydrolyzed to pentoses, then undergo-

ing cyclodehydration (→Furan and Deriva-tives, Chap. 3.).

Similarly accessible by acid-induced elimi-nation of three moles of water fromfructoseorinulin hydrolysatesis 5-hydroxymethylfurfural(HMF) [26], [53].

When using nonaqueous conditions, e.g.,DMSO as the solvent and a strongly acidicresin, the fructose part of disaccharides such asisomaltulose can similarly be converted intothe respective, glucosylated HMF-derivative(GMF) without cleaving the acid-sensitive gly-cosidic linkage [54].

The trisaccharideraffinose, a storage carbo-hydrate in many plants can be cleaved enzy-matically withα-galactosidase into sucrose andgalactose. This reaction is used in the beet sugarindustry to increase the yield of sucrose, as wellas to improve the digestibility of food fromleguminous plants. Raffinose can also be fer-


mented by baker’s yeast to form melibiose (α-D-Galp-(1→6)-D-Glcp).

6.2. Isomerization

Under basic conditions aldoses isomerize totheir C-2 epimers and the corresponding ke-toses. Specific conditions may be appliedfor the preparation of particular products. In0.035 % aqueous sodium hydroxide at 35◦Cfor 100 h, for example, either of the threefollowing sugars is converted into an equi-librium mixture containingD-glucose (57 %),D-fructose (28 %), andD-mannose (3 %).This interconversion is known as theLobryde Bruyn – van Ekenstein rearrangement[55],which occurs by enolization of either sugarto the 1,2-enediolate – the mechanism beingbest visualized in the Fischer projection formu-lae (Fig. 19). In favorable cases alkali-promotedstereoisomerizations can be of preparative use,especially when the starting sugar is relativelyabundant and when structural features mini-mize competing reactions. Thus lactulose canbe satisfactorily made by epimerization of lac-tose (→Lactose and Derivatives, Chap. 2.1.2.),or maltulose from maltose [56], [57], using ei-ther sodium hydroxide alone or with borate oraluminate as coreagents.

Figure 19.Lobry de Bruyn – van Ekenstein rearrangement

Alternatively, C-2-epimerization without ke-tose involvement can be induced by use of

molybdate under mildly acidic conditions. Thisremarkable transformation (Bilik reaction) [58]involves a C-1 / C-2 interchange within the car-bon skeleton.

6.3. Decomposition

Exposure of carbohydrates to high tempera-tures leads to decomposition (dehydration) withdarkening (caramelization). This can be usedto produce the caramel color, e.g., the colorof cola beverages. Thermal decomposition inthe presence of amino acids (Maillard reaction[59]) is responsible for many color- and flavor-forming reactions, such as in baking of breadand roasting of meat or coffee. The highly com-plex Maillard reaction, elicited during cookingor the preservation of food, involves condensa-tions, Amadori-type rearrangements of glyco-sylamine intermediates, and degradations. Thedark-colored products formed are responsiblefor the nonenzymic browning observed withvarious foodstuffs.

7. Reactions at the Carbonyl Group

In solution, reducing sugars establish an equi-librium between their pyranoid and furanoidhemiacetal forms via the open-chain carbonylspecies. Although the latter is present only toa very minor extent, equilibration between thedifferent forms is fast, so that reducing sugarsundergo the typical carbonyl reactions withO-,N-, S-, andC-nucleophiles.

7.1. Glycosides

With alcohols in the presence of acid catalystsreducing sugars give the respective full acetals,called glycosides (Fischer glycosidation) [60].Depending on the distribution of furanoid andpyranoid tautomeric forms in the reaction mix-ture, not only glycosides with different ringsizes, i.e., glycopyranosides and glycofurano-sides, can result, but also theα- andβ-anomersof each. Thus, whenD-glucose is heated withmethanol in the presence of anhydrous hy-drogen chloride, pure crystalline methylα-D-glucopyranoside can be isolated in 90 % yield,


whilst the same reaction withD-galactose yieldsa mixture of the two furanoid and pyranoidmethyl galactosides, from which the methylα-D-galactopyranoside can be obtained in crys-talline form in 41 % yield only.

Although the Fischer glycosidation presentsone of the easiest means for preparing gly-cosides, synthesis of more complex membersof this series, particularly the construction ofthe biologically important heterooligosaccha-rides widely distributed in nature, requiresthe use of more sophisticated methodolo-gies. These preparative techniques generally in-volve the coupling of suitably OH-group pro-tected glycosyl donors (i.e., glycosides with ananomeric leaving group) with an alcohol com-ponent – usually a mono-, di-, or oligosac-charide in which the hydroxyls carry protect-ing groups [61] except for the one to be gly-cosylated (‘the glycosyl acceptor’). Effectiveglycosyl donors, derived fromD-glucose, arelisted in Table 1. They represent the presentlymost suitable donors for achieving glycosidicbond-forming reactions with high stereocon-trol: glycosyl chlorides and bromides [62],2-oxoglycosyl bromides [63], [64], anomericphosphates [65] and trichloracetimidates [66],thioglycosides [67], glycosyl sulfoxides [68],and 1,2-anhydrides [69], some of these method-ologies being amenable to combinatorial andsolid phase synthesis [70].

Table 1.Established glycosyl donors for the stereoselective synthe-sis of oligosaccharides

Glycosyl halides, X = Cl, Br Ulosyl bromides

Glycosyl trichloroacetimidates Thioglycosides

Glycosyl sulfoxides 1,2-Anhydro-sugars(R = acetyl, benzoyl, benzyl)

For further details on this subject, presentlyunder intense further exploration, some recentgeneral treatments [29], [71–73] are recom-mended.

7.2. Thioacetals and Thioglycosides

Sugars react rapidly with alkanethiols in thepresence of acid catalysts at room tempera-ture to give acyclic dialkyl dithioacetals as themain products [74], and therefore the reaction ismarkedly different from the Fischer glycosida-tion. These open-chain compounds can be usedto prepare monosaccharide derivatives with afree carbonyl group, such as 2,3,4,5,6-penta-O-acetyl-D-glucose:


1-Thioglycosides, established glycosyldonors in oligosaccharide syntheses (upon ac-tivation with methyl trifluoromethanesulfonateor other promoters), have to be prepared indi-rectly, e.g., from peracylated pyranoses (or their1-halides) by exposure to thiols in the presenceof BF3 etherate or zinc chloride:

7.3. Glycosylamines, Hydrazones, andOsazones

Aldoses condense with ammonia and with pri-mary and secondary amines upon loss of wa-ter – reactions that are analogous to the Fischerglycosidation. The initial condensation prod-ucts appear to be the open-chain aldimineswhich then cyclize to theglycosylamines–also calledN-glycosides, Thereby, the pyranoseforms are preferentially adopted as these arethermodynamically more stable. Accordingly,D-glucose reacts with aniline in methanol to theα- andβ-N-glucopyranosides:

Acids also catalyze a transformation calledthe Amadori rearrangement[75] which of-ten accompanies attempts to prepare glycosy-lamines from aldoses and amines. This reactionis related to theLobry de Bruyn-van Ekensteinreaction of aldoses involving the rearrange-ment ofN-alkylamino-D-glucopyranosides into1-alkylamino-1-deoxy-D-fructoses (Fig. 20).

Figure 20.Amadori rearrangement of glycosyl amines in-duced by acid catalysis:D-Glucopyranosylamine is con-verted into 1-alkylamino-D-fructose [74]

Glycosylamine derivatives are probably in-volved in the complex Maillard reaction [59],whereby sugars, amines, and amino acids (pro-teins) condense, rearrange, and degrade dur-ing cooking or the preservation of food. Hy-drazones and osazones result when aldoses orketoses are reacted with hydrazine or arylhy-drazines, the product depending on the con-ditions used [76]. With hydrazine acetate inhighly acidic medium in the cold, hydrazonesare formed, which initially adopt the acyclicstructure, but tautomerize in aqueous solutionto the cyclic glycosylhydrazine forms. How-ever, when free sugars are treated with an ex-


cess of phenylhydrazine, the reaction proceedsfurther to give – in a formal oxidation of thevicinal 2-OH – the highly crystalline, water-insoluble phenylosazones which contain twophenylhydrazine residues per molecule, witha third phenylhydrazine molecule being con-verted into aniline and ammonia. As C-2 of asugar is involved in this process,D-glucose,D-mannose, andD-fructose yield the same prod-uct:

This result played a fundamental role in EmilFischer’s elucidation of the configurational in-terrelationships of the sugars, eventually lead-ing [10], [11] to the sugar family trees depictedin Figures 3 and 4.

7.4. Chain Extension

The carbonyl group offers excellent opportuni-ties for extension of the sugar chains and theformation of ‘higher’ sugars. However, only afew carbon nucleophiles can be applied directlyto the free sugars, i.e., without protection of theOH groups. The classical methods comprise theaddition of cyanide ion (Kiliani – Fischer ex-tension) [77] and of nitromethane under suit-able alkaline conditions [78]. In either case, thecyano and nitromethylene group newly intro-duced can be converted into an aldehyde func-tionality by hydrolysis of the diastereomericcyanohydrins to aldonic acids, lactonizationand subsequent reduction, or by applying theNef reactionto the nitroalditols, thus provid-ing methods for ascent of the sugar series. Forexample, the rare sugarD-allose can be readilyprepared fromD-ribose [79] (Fig. 21), whereasthe nitromethane addition approach allows theacquisition of the equally scarce hexosesL-glucose andL-mannose fromL-arabinose [80](Fig. 22).

Figure 21. The Kiliani – Fischer cyanohydrin synthesiswith D-ribose: the approximate 1:1 mixture of the 2-epimeric D-allo- and D-altro-cyanohydrins can be sepa-rated at the aldonic acid stage, subsequent reduction of theD-allonic acid in the form of its 1,4-lactone then providingD-allose (34 % overall yield)

Figure 22. Nitromethane addition toL-arabinose in al-kaline medium generates a mixture of the 2-epimericL-nitroalditols (ofL-glucoandL-mannoconfiguration) whichupon separation are subjected to the Nef reaction [78]

A special case of chain extension by ni-tromethane is the cyclization of sugar-deriveddialdehydes – readily and quantitatively ob-tained from anomerically blocked glycopyrano-sides or furanosides by periodate oxidation – togive 3-nitrosugars [81], [82]. As exemplified formethyl β-D-glucopyranoside (Fig. 23), a mix-ture of 3-nitrohexosides is primarily obtainedfrom which the major product, theD-gluco iso-mer crystallizes. Subsequent catalytic hydro-genation then provides the 3-amino-3-deoxy-D-glucoside [83].


Figure 23.Conversion of methylβ-D-glucoside into its 3-amino-3-deoxy-derivative via the dialdehyde-nitromethanecyclization approach [81]

This nitromethane cyclization sequence canbe extended to nitroalkanes, e.g., nitroethaneor even nitroacetate [84], thus providing aready access – upon hydrogenation of the nitrogroup – to 3-methyl- or 3–carboxy-branched 3-aminosugars.

7.5. Chain Degradation

The removal of a terminal carbon atom froma sugar or sugar derivative to leave an alde-hyde group is realizable in a variety of waysbut the yields are often poor. The most prac-tical approach involves conversion of an al-dose to the corresponding dialkyl dithioac-etal (mercaptal) by reaction with an alka-nethiol, then oxidation to the bis-sulfone witha peracid. Treatment of the bis-sulfone withdilute ammonia causes expulsion of the sta-bilized bis(ethylsulfonyl)methyl carbanion andgives the aldose with one carbon atom less.This three-step protocol smoothly convertsD-glucose, for example, intoD-arabinose [85]:

7.6. Reductions to Alditols

Aldoses and ketoses can readily be reduced toalditols (Table 2) with the generation of a newalcoholic group from the carbonyl functions,their names being derived from the respectivealdose by replacing the ‘ose’ suffix with ‘itol’.Thus, reduction ofD-glucose givesD-glucitol.Originally, sodium amalgam was the reducingagent most commonly used for these reduc-tions, but now it has been superseded by oth-ers, particularly sodium borohydride in aque-ous solution, or for alkali-sensitive sugars, byNaBH3CN in acetic acid. High pressure hydro-genation of aldoses and ketoses over rare metalcatalysts, especially nickel is used for the com-mercial preparation of alditols (→Sugar Alco-hols).


Table 2.Low-caloric, non-cariogenic sugar alcohol sweeteners, ob-tained by catalytic hydrogenation of the parent aldoses. Recom-mended nomenclature [48] for sorbitol isD-glucitol (henceD-Glc-ol). Being amesocompound, xylitol requires noD- or L-prefix .

D-Glucitol Maltitol(Sorbitol) (α-D-Glc-(1→4)-D-Glc-ol)(D-Glc-ol)

D-Mannitol Lactitol(D-Man-ol) (α-D-Gal-(1→4)-D-Glc-ol)

Xylitol(Xyl-ol)

Isomalt(α-D-Glc-(1→6)-D-Glc-ol

(α-D-Glc-(1→4)-D-Man-ol)

D-Glucitol [50-70-4] (→Sugar Alcohols,Chap. 3.), common name sorbitol, produced ata level of 900 000 t/a worldwide, has a sweettaste and is used in foods for diabetics [86],[87]. It is also the synthetic precursor for ascor-bic acid (vitamin C), with about 20 % of theannual production sorbitol going to this use.Sorbitol is used as a humectant in cosmeticand pharmaceutical formulations and in foods.It is also applied as an alcoholic componentin the preparation of rigid polyurethane foams.Fatty acid esters of monoanhydrosorbitol (1,4-sorbitan) are widely used as emulsifiers andnon-ionic surfactants. The mono- and dinitrate

esters of 1,4 : 3,6-dianhydrosorbitol (isosorbide[652-67-5]) are coronary vasodilators.

D-Mannitol [87-78-5] (→Sugar Alcohols,Chap. 4.), is prepared by hydrogenation ofthe fructose portion of invert sugar [86], [88],which yields a mixture of mannitol and sorbitol.In contrast to sorbitol, mannitol is not hygro-scopic; world production in 2000 was approxi-mately 30 000 t. Mannitol is used in the manu-facture of dry electrolytic condensers and syn-thetic resins; in the pharmaceutical industry as adiluent for solids and liquids and in the prepara-tion of the vasodilator mannitol hexanitrate; inthe food industry as an anticaking and free-flowagent, and as a lubricant, stabilizer, and nutri-tive sweetener.

Other sugar alcoholsmostly used assweeteners, arexylitol, obtained by catalytichydrogenation ofD-xylose, which in turn isacquired from wood xylans or maize cobs byacid hydrolysis, and a series of disaccharide al-cohols, each manufactured analogously fromthe respective parent disaccharide:maltitol(from partially hydrolyzed starch syrup; Ly-casin [88] contains a high proportion thereof),lactitol and, most notably,isomalt, which dueto its mild, pleasant sweetness, ready crystal-lizability and excellent thermal stability ap-pears presently the most prevailing. Isomalt,also called “Palatinit”, consists of an approx-imate 1:1 mixture ofα-D-glucosyl-(1→6)-D-sorbitol and α-D-glucosyl-(1→1)-D-mannitol(see Table 21). The latter forms a dihydrate,the two water molecules being attached to themannitol portion in a hydrogen-bonded waterbridge [89]. Isomalt is produced from sucrosethroughProtaminobacter rubrum-induced iso-merization to isomaltulose (‘palatinose’) andsubsequent catalytic high-pressure hydrogena-tion (→Sugar Alcohols, Chap. 5.2.).

7.7. Oxidation

Controlled stoichiometric oxidations of carbo-hydrates to yield glyconic acids or their deriva-tives are limited to aldoses. Such oxidations canbe carried out almost quantitatively either en-zymatically by dehydrogenases or oxidases orchemically with bromine or iodine in buffered


solution. Under these conditions,D-glucose –through its pyranose form prevailing in solu-tion – is directly converted into the 1,5-lactoneof D-gluconic acid (i.e., the internal ester ratherthan the free acid), which on addition of base isconverted to the salt (in open-chain form). How-ever, by crystallization from aqueous solutionit is possible to obtain the free acid or the 1,4-lactone. For different aldonic acids the amountsof each form present at equilibrium vary withstructure and with pH of the solution, in con-trast to the free sugars, the five-membered ringlactones are relatively favored.

Strong nitric acid appears to be one of thefew oxidants which is able to also oxidize theterminal primary hydroxyl group of aldosesbut leave the secondary hydroxyl groups un-changed.D-Glucose treated with this reagentgives D-glucaric acid [90], its name being de-rived by replacing the ending ‘ose’ in the sugarby ‘aric acid’. Aldaric acids can form mono-or dilactones, in the case ofD-glucaric acid,the well crystallizing form is the furanoid 1,4-lactone:

Under the influence of very strong oxidiz-ing agents such as potassium dichromate or per-manganate, sugars suffer oxidative degradation.Hence, these agents are of no preparative use.

8. Reactions at the Hydroxyl Groups

8.1. Ethers

The most simple compounds of this type aremethyl etherswhich occur in a range of nat-ural carbohydrates. Methyl esthers belong tothe most stableO-substituted sugar derivatives,such that per-O-methylated hexoses can even bedistilled. Traditionally, the labeling of free OH-groups in polysaccharides is effected by methy-lation, structural analysis being then based onthe O-methyl sugars obtained on hydrolysis.Methyl ethers are conveniently prepared frommethyl bromide, iodide, or sulfate in polar apro-tic solvents such as dimethylformamide or di-methylsulfoxide. Agents for deprotonation ofthe hydroxyl group and for binding the min-eral acids liberated include alkali hydroxides orhydrides and barium or silver oxide. With highmolecular mass carbohydrates, quantitative de-protonation is best carried out with sodium orpotassium methylsulfinyl methanide (the conju-gate base of dimethyl sulfoxide) [91].

Benzyl ethersare amongst the most com-monly used protecting groups in carbohydratechemistry [92], as theO-benzyl moiety is eas-ily removed by hydrogenolysis (Pd/C, H2) to


yield the respective alcohol and toluene [61].For the preparation of benzyl ethers, traditionalmethods involve such reagents as benzyl halidesin combination with sodium hydroxide, sodiumhydride, or silver oxide.

Triphenylmethyl (trityl) ethersare usedmainly for the temporary substitution of pri-mary hydroxyl groups and are usually preparedusing trityl chloride in pyridine. Under mildacidic conditions, e.g., acetic acid or boron tri-fluoride in methanol, the trityl ethers are readilycleaved.

Trimethylsilyl ethers, although extremelysensitive both to base- and acid-catalyzed hy-drolysis, are often used in analytical andpreparative carbohydrate chemistry. The per-trimethylsilyl ethers of monosaccharides andsmall oligosaccharides are relatively volatile,highly lipophilic, and thermostable, and there-fore, ideal derivatives for gas chromatographicanalysis. The trimethylsilyl ethers are rapidlyformed in pyridine by using a mixture ofhexamethyldisilazane and trimethylchlorosi-lane [93].

Cellulose ethers(→Cellulose Ethers) aregenerally manufactured by the Williamson syn-thesis: reaction of sodium cellulose (preparedby treating cellulose with 20 to>50 %sodium hydroxide) with an organic halidesuch as chloromethane or sodium monochloro-acetate. The latter reagent produces sodiumcarboxymethyl cellulose (NaCMC), which iswidely used, for example, as a thickening agentin foods. Worldwide production of NaCMC isin the range of several hundred thousand tonsper year.

8.2. Esters of Inorganic Acids

Phosphoric acid estersof sugars play vi-tal roles in such fundamental processes as thebiosynthesis and metabolism of sugars and,hence, are present in every organism, the mostimportant esters beingD-glucose 1-phosphate[59-56-3], D-glucose 6-phosphate [56-73-5],and D-fructose 1,6-diphosphate [488-69-7]. Inaddition, phosphates ofD-ribose and its 2-deoxy derivative form fundamental componentsof ribonucleic acid (RNA) and deoxyribonu-cleic acid (DNA) and of various coenzymes(→Nucleic Acids).

α-D-Glucose-1-phosphate D-Glucose-6-phosphate

D-Fructose-1,6-diphosphate D-Ribose-5-phosphate

2-Deoxy-D-ribose-5-phosphate Adenosine-5-phosphate(AMP)

Both chemical and enzymic methods areavailable for the synthesis of specific phos-phates. Chemically, anomeric phosphate es-ters are usually prepared either from glycosylhalides or other glycosyl donors by reactionwith silver dibenzyl phosphate, whilst phos-phorylation of nonanomeric hydroxyl groupsis effected with specifically blocked sugarderivatives and diphenyl or dibenzyl phos-phorochloridate [94]. Biochemically, phos-phates are produced by the action of phos-phatases on provided substrates [95].

Sulfate Esters.Sulfate groups are present inmany biologically important polysaccharides,such as heparin and chondroitin sulfate. Sul-fated monosaccharides can be prepared fromsuitable monosaccharide derivatives by reactionwith chlorosulfuric acid in pyridine [96].

Nitrate estersof carbohydrates [97] are notfound in nature, yet a large variety ranging frommonoesters to peresters have been prepared, fa-vorable conditions being cold nitric acid/aceticanhydride for nonanomeric OH groups, whilstanomeric nitrate esters are accessible via re-action of acyl glycosyl halides with silver ni-trate. Sugar mono- and dinitrates are stablecrystalline compounds, such as, e.g., adenosine


mononitrate (AMN), the nitrate analog to AMP[98], and the dinitrate of 1,4:3,6-dianhydro-D-glucitol (‘isosorbide dinitrate’), which is inbroad pharmaceutical use as a coronary va-sodilator [99]:

Adenosine 5-nitrate (AMN) Isosorbide dinitrate

More highly substituted derivatives are heatand shock sensitive, such as, e.g., mannitol hex-anitrate or nitrate esters of cellulose (nitrocel-lulose). These contain as many as three ONO2

groups per glucose unit. The product with about13 % nitrogen is the well-known guncotton(→Cellulose Esters, Chap. 1.), whereas cellu-loid is nitrocellulose containing about 10 % ni-trogen plasticized with camphor; it is one of theoldest known plastics. This plastic was once theprincipal photographic and movie film, but hasbeen replaced by other films because of its highflammability.

8.3. Esters of Organic Acids

For the esterification of the hydroxyl group offree or partially otherwise blocked sugars, acylhalides or acid anhydrides are usually used, e.g.,acetic anhydride/sodium acetate or zinc chlo-ride or acetic anhydride/pyridine readily yieldthe respectiveperacetates.

Perbenzoylationcan be effected with ben-zoyl chloride in pyridine or benzoyl cyanidein acetonitrile with triethylamine as the cata-lyst. Tertiary OH groups, present in ketoses orbranched-chain sugars, usually require the ad-dition of 4-(dimethylamino)pyridine.

Whereas peracetates and perbenzoates ofsimple sugars are important intermediates forthe preparation of the respective glycosylhalides and, hence, acylated glycals and hy-droxyglycals (see Section 8.4), those of somepolysaccharides are of industrial relevance. Ac-etate esters of cellulose are manufactured on a

large scale, whereby the degree of acetylationdetermines the solubility and use: the triacetate(3.0-acetate) is soluble in chloroform, the 2.5-acetate in acetone, and the 0.7-acetate in wa-ter. These esters, as well as mixed cellulose ac-etate/propionate and acetate/butyrate are widelyused in the production of lacquers, films, andplastics (→Cellulose Esters, Chap. 2.1.).

Polysaccharide estersin which the carbohy-drate portion is the acid component occur inthe plant kingdom in fruits, roots, and leaves.For example,pectinsare high molecular masspolygalacturonic acids joined byα-(1→4)-glycosidic links, in which some of the car-boxylic acid groups are esterified with methanol(→Polysaccharides, Chap. 3.). In the produc-tion of fruit juices the formation of methanol,which can be liberated through the action ofpectinesterases, should be avoided. Pectins inwhich 55 – 80 % of the carboxyl groups are es-terified are called high-methoxyl pectins (HM-pectins), and have the important property ofgelling at very low concentrations (≈0.5 %)in water in the presence of sugars and acid.Low-methoxyl (LM, <50 % of the carboxylgroups esterified) pectins form gels with diva-lent cations such as a Ca2+; 0.5 % of a low-methoxyl pectin can bind 99.5 % of the waterin the gel matrix. These pectins can be used asgelling agents in the production of jellies fromfruit juices.

8.4. Acylated Glycosyl Halides

Per-O-acylated monosaccharides can be con-verted smoothly into glycosyl halides by dis-solving them in cold solutions of the hy-drogen halide in glacial acetic acid (ac-etates of acid-sensitive oligosaccharides mayundergo cleavage of glycosidic bonds). Be-cause of the dominance of the anomeric ef-fect in the pyranosyl cases, the anomer withaxial halide is substantially preferred. Ac-cordingly, on acylation and subsequent HBr-treatment, usually performed as a one potoperation, D-glucose yields the 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (‘aceto-bromoglucose’, R = Ac in Fig. 24) or its ben-zoylated, pivaloylated (R =tert-BuCO) or ben-zylated (R = C6H5CH2) analogues [62]. Thesehalides are commonly used directly for gly-


cosylation reactions, which is the basis of thetraditional Koenigs-Knorr procedure [100], orconverted into more elaborated glycosyl donors(see Table 1).

Glycosyl halides are also of significance interms of the use of monosaccharides as inex-pensive enantiopure starting materials for theconstruction of complex, non carbohydrate nat-ural products [101–103], which usually requirethe reduction of the number of chiral cen-ters paired with the introduction of olefinicor carbonyl unsaturation. Treatment of glyco-syl halides with zinc/acetic acid [104] – or,preparatively more efficient zinc/1-methylimid-azole in ethyl acetate under reflux [105] –results in reductive elimination to give theglycal, in Figure 24 illustrated with the for-mation of tri-O-acetyl-D-glucal. Simple 1,2-elimination of hydrogen bromide using diethy-lamine in acetonitrile in the presence of tetra-butylammonium bromide or by 1,8-diazabicy-clo[5.4.0]undec-7-ene (DBU) in DMF [106],[107] yields the respective 2-hydroxyglycal es-ters. TheD-glucose-derived benzoylated exam-ple in Figure 24 is an ester of the enol form of1,5-anhydro-D-fructose.

Figure 24.Formation of glycosyl and 2-oxoglycosyl (‘ulo-syl’) bromides from peracylated monosaccharides, as ex-emplified for theD-glucose case, and their conversions intoglucal and 2-hydroxyglucal esters

Endowed with high crystallinity and shelfstability, the hydroxyglycal esters are of con-siderable preparative interest not only for thegeneration of a plethora of other unsaturatedcompounds, e.g., pyranoid enones [108] andenolones [102], [109], but also as precursors forthe highly versatile ulosyl bromides, producedin high yields simply by exposure to NBS orbromine in the presence of ethanol [110], [111].The utility of these ulosyl bromides as glycosyldonors in the straightforward synthesis ofβ-D-mannosides has been amply demonstrated [62],[63], [112].

8.5. Acetals

Acetals are generally derived from the reac-tion of an aldehyde or ketone – benzaldehydeand acetone being the most common – with ageometrically suitable diol grouping, of whichthere is a large variety in free sugars, glyco-sides, and alditols [113–115]. The reactions arenormally carried out in the reagent aldehydeor ketone as solvent with an electrophilic cat-alyst (H2SO4 or ZnCl2). Acetal formation un-der these conditions is thermodynamically con-trolled and usually very specific. Ketones suchas acetone or cyclohexanone predominantlybridge vicinal diols to form five-memberedcyclic products (1,3-dioxolanes) as exemplifiedby the di-O-isopropylidene derivatives ofD-glucose (‘diacetone-glucose’),D-galactose andD-mannitol:


1,2:5,6-Di-O-isopropylidene-α-D-glucofuranose

1,2:4,5-Di-O-isopropylidene-α-D-galactopyranose

1,2:5,6-Di-O-isopropylidene-D-mannitol

Methyl 4,6-O-benzylidene-α-D-glucopyranoside

Methyl 4,6-O-benzylidene-α-D-galactopyranoside

Aldehydes, however, show a distinct pref-erence for 1,3-diols, as illustrated by the six-membered 4,6-O-benzylidene acetals of methylD-glucoside andD-galactoside.

Introduction of cyclic acetal groups into sug-ars is simple and satisfactory in terms of yields.As cyclic acetals are stable towards alkali, theentire armory of organic reactions requiringbasic conditions can be applied, and due totheir ready removal with mild acid (e.g., 90 %aqueous trifluoroacetic acid at room tempera-ture), they provide indispensable intermediatesin preparative carbohydrate chemistry.

9. Carbohydrates as Organic RawMaterials

As our fossil raw materials are irrevocably de-creasing – the end of cheap oil is realisti-cally prognosticated for 2040 at the latest [116–118] – and as the pressure on our environ-ment is building up, the progressive changeoverof chemical industry to renewable feedstocksemerges as an inevitable necessity [118], [119].

The terrestrial biomass is considerably morecomplex than fossil raw materials, constitutinga multifaceted accumulation of low and high

molecular mass products. Carbohydrates, themost abundant of these materials, aside theirtraditional uses for food, lumber, paper andheat, are the major biofeedstocks to developindustrially and economically viable organicchemicals that are to replace those derived frompetrochemical sources.

The bulk of the annually renewablecarbohydrate-biomass consists of polysaccha-rides, yet their nonfood utilization is confined totextile, paper, and coating industries, either assuch or in the form of simple esters and ethers.Organic commodity chemicals, however, arelow molecular mass products; hence, they aremore expediently acquired from low molecularmass carbohydrates than from polysaccharides.This in turn means that polysaccharides usu-ally must be hydrolyzed before being furtherprocessed to organic commodity chemicals.

Table 3 lists the availability and bulk-quantity prices of the eight least expensive sug-ars – all well below¤10/kg – as comparedto some sugar-derived compounds and basicchemicals from petrochemical sources. The re-sult is stunning, since the five cheapest sugars,some sugar-alcohols, and sugar-derived acidsare not only cheaper than any other enantiop-ure product, such as hydroxy- or amino acids,but they compare favorably with basic organicbulk chemicals such as acetaldehyde or aniline.Actually, the first three of these sugars, sucrose,glucose, and lactose, are in the price range ofsome of the standard organic solvents.


Table 3. Annual production volume and prices of simple sugars,sugar-derived alcohols, and acids as compared to some petrochem-ically derived basic chemicals and solvents

World production∗, t/a Price∗∗, ¤/kg

SugarsSucrose 130 000 000 0.30D-Glucose 5 000 000 0.60Lactose 295 000 0.60D-Fructose 60 000 1.00Isomaltulose 50 000 2.00Maltose 3000 3.00D-Xylose 25 000 4.50L-Sorbose 60 000 7.50Sugar alcoholsD-Sorbitol 900 000 1.80D-Xylitol 30 000 5.00D-Mannitol 50 000 8.00Sugar-derived acidsD-Gluconic acid 60 000 1.40L-Lactic acid >100 000 1.75Citric acid 500 000 2.50L-Tartaric acid 35 000 6.00Amino acidsL-Lysine 40 000 5.50L-Glutamic acid 500 000 7.00Basic chemicalsAniline 1 300 000 0.95Acetaldehyde 900 000 1.15Adipic acid 1 500 000 1.70SolventsMethanol 25 000 000 0.15Toluene 6 500 000 0.25Acetone 3 200 000 0.55

∗ Reliable data are only available for the world production ofsucrose, the figure given referring to the crop cycle 2000/2001[23]. All other data are average values based on estimates fromproducers and/or suppliers, as the production volume of manyproducts is not publicly available.∗∗ Prices given are those attainable in early 2002 for bulkdelivery of crystalline material (where applicable) based onpricing information from sugar industry (sugars) andTheChemical Market Reporter2002, no. 2, 16 – 19 (acids, basicchemicals, and solvents). The listings are intended as abenchmark rather than as a basis for negotiations betweenproducers and customers. Quotations for less pure products are,in part, sizably lower, e.g., for the commercial sweetener “highfructose syrup”, which contains up to 95 % fructose, and, thus,may readily be used for large-scale preparative purposes.

Despite their large-scale accessibility, chem-ical industry, at present, utilizes these mono-and disaccharides only to a minor extent asfeedstock for organic chemicals. This is am-ply documented by the fact that of the 100 ma-jor organic chemicals manufactured in the USAin 1995 [120], only seven were derived frombiofeedstocks, and five of these – ethanol, sor-bitol, citric acid, lysine, and glutamic acid –used carbohydrates as the raw material source.Intense efforts within the last decade to boostthe production of organic chemicals from thesugars in Table 3 [121–127] have not basicallychanged this picture.

There are various reasons for that: at present,the use of fossil raw materials is more economicand the process technology for conversion ofpetrochemical raw materials into organic chem-icals is exceedingly well developed and basi-cally different from that required for transform-ing carbohydrates into products with industrialapplication profiles. This situation originatesfrom the inherently different chemical struc-tures of the two types of raw materials, of whichthe essence is manifested in their structure-based names.

Fossile Resources: Renewable Resources:

HYDRO-CARBONS CARBO-HYDRATESCnH2n+2 Cn(H2O)n

oxygen-free, overfunctionalized withlacking functional groups hydroxyl groups

Our fossil resources arehydrocarbons, dis-tinctly hydrophobic, oxygen-free, and lackingfunctional groups, annually renewables arecar-bohydrates, overfunctionalized with hydroxylgroups and pronouncedly hydrophilic in nature.Needless to say, that the methods required forconverting carbohydrates into viable industrialchemicals are diametrically opposed to thoseprevalent in petrochemical industry: microbialtransformations or chemical processing with re-duction of oxygen content and introduction ofC=O and/or C=C unsaturation, or preferablyboth.

9.1. Microbial Synthesis

Microbial processing by direct fermentation ofcarbohydrates can be used to synthesize a largenumber of organic chemicals, yet only a fewhave clearly reached commodity status. Theyare ethanol (fermentation ethanol as distin-guished from synthetic ethanol produced by hy-dration of ethylene),citric acid (from molassesby Aspergillus niger), glutamic acidandlysine(from glucose byBrevibacterium lactofermen-tum and others), andgluconic acid(from glu-cose byGluconobacter suboxydans). Together,these chemicals have a sizable annual produc-tion (cf. Table 3), however, questions of howand when other microbially synthesized com-modity chemicals will play a larger role in


the world’s chemical markets remain to be an-swered.

By contrast, there is a broad range of spe-cialty chemicals that are manufactured todayby microbial conversion of carbohydrate feed-stocks, usually products with molecular struc-tures too complex for conventional chemicalsynthesis. Examples are antibiotics (penicillins,kanamycins, tetracyclins) and vitamin C, B2 (ri-boflavin), and B12 (cyanocobalamin). The pos-sibility, however, for production of further high-value-added specialty chemicals or pharmaceu-ticals from carbohydrates is almost unlimited aslong as the appropriate organism and substrateare allowed to interact under suitable conditions[128].

9.2. Chemical Conversions

Presently, the dominant methods of convertingcarbohydrates to organic chemicals – be it bulk,intermediate or fine chemicals, pharmaceu-ticals, agrochemicals, high-value-added spe-cialty chemicals, or simply enantiopure build-ing blocks for organic synthesis – are chemical.

9.2.1. Furan Derivatives

Furfural appears to be the only large-volume chemical (200 000 t/a) produced fromcarbohydrate sources, usually agricultural andforestry wastes [51], [52] (→Furan and Deriva-tives, Chap. 3.). Due to its ready accessibility,the ensuing chemistry of furfural is well de-veloped, providing a host of highly versatileindustrial chemicals by simple straightforwardoperations (Fig. 25): furfuryl alcohol and itstetrahydro derivative by hydrogenation of fur-fural, furfurylamine through reductive amina-tion, furoic acid by oxidation, and furanacrylicacid (Perkin reaction) or furylidene ketones viaaldol condensations. Furfural is also the keychemical for the commercial production of fu-ran (through catalytic decarbonylation) and oftetrahydrofuran by hydrogenation, thereby pro-viding a biomass-based alternative to its petro-chemical production via dehydration of 1,4-butanediol. Further importance of these fu-ranic chemicals results from their ring-cleavagechemistry, which has led to a variety of other

established chemicals, e.g., levulinic acid (4-oxovaleric acid) and maleic anhydride [52],[129].

The bulk of the furfural produced is used asfoundry sand linker in the refining of lubricatingoil, and, together with furfurylalcohol and itstetrahydro derivative, enters into condensationswith formaldehyde, phenol, acetone, or urea toyield a variety of resins of complex, ill-definedstructures, yet excellent thermosetting proper-ties, most notably high corrosion resistance, lowfire hazard and extreme physical strength [52],[130].

5-(Hydroxymethyl)furfural (HMF). Likemany petroleum-derived basic organic chem-icals, e.g., adipic acid and hexamethy-lenediamine, 5-hydroxymethylfurfural (HMF)is a six-carbon commodity with high industrialpotential, and, thus, has been termed “a keysubstance between carbohydrate chemistry andmineral oil-based industrial organic chemistry”[26]. It is readily accessible from fructose, orinulin hydrolysates by acid-induced elimina-tion of three moles of water [53] and even apilot-plant process has been developed [26].

Of high industrial potential as intermedi-ate chemicals are the various HMF-derivedproducts (Fig. 26), for which well worked-out, large scale-adaptable production proto-cols are available. Of these products, 2,5-bis(hydroxymethyl)furan, 5-hydroxymethyl-2-furoic acid, and the 2,5-dicarboxylic acidhave extensively been exploited for the prepa-ration of furanoic polyesters [136]. Thediol has been reacted with various aliphaticand aromatic diacids; the ethyl ester of 5-hydroxymethylfuroic acid, upon polycondensa-tion, gave a mixture of linear and cyclic prod-ucts, whereas the furan diacid has been poly-esterified with a series of aliphatic diols orbisphenols. Even an all-furanic polyester hasbeen successfully prepared from its respectivemonomeric components [136].


Figure 25.Versatile furanic commodity chemicals derived from pentosans in agricultural wastes (corn cobs, oat hulls, woodchips, bagasse)

Figure 26.Versatile intermediate chemicals derived from hydroxymethylfurfural (HMF)

Key A Ag2O, 100◦C,75 % [130]

E Pt, C / H2, quant. [132]

B BaMnO4, 93 %[130]

F Ni/H2, NH3, 72 % [133]

C NH2OH, thenNi/H2, 33 %[130]

G Pt, C / O2, pH 7. 91 %[134]

D TsOH (H2O↑),89 %[131]


Another obvious outgrowth from thefuran-2,5-dicarboxylic acid and the respec-tive diamine was the generation of furanicpolyamides, as they could potentially re-place adipic or terephthalic acid, and, corre-spondingly, hexamethylenediamine orp-diami-nobenzene in polyamides (see Section 9.2.5).

Despite this impressive array of usefulHMF-derived intermediate chemicals, it is, asof now, not produced on an industrial scale. Ob-viously, the economic preconditions are not yetfavorable enough. A recent assessment of theeconomics of HMF against competitive petro-chemical raw materials [137] gives ample ev-idence thereof: prices of naphtha and ethyleneare in the¤150 – 400/t range, those of crudeinulin or fructose (≈ ¤1000/t) give rise to anHMF-marketing price of at least¤2500 perton – too expensive at present for a bulk-scaleindustrial product. Accordingly, as long as theeconomic situation favors fossil raw materials,applications of HMF lie in high value-addedproducts, such as pharmaceuticals or specialniche materials. Prototype for this outlet is Ran-itidine [138], an efficient antiulcer drug due toits potent oral inhibition of histamine-inducedgastric acid secretion:

Ranitidine

Furans with a Tetrahydroxybutyl SideChain. Another simple, one-step entry fromhexoses to more highly substituted furans in-volves their ZnCl2-mediated reaction with 1,3-dicarbonyl compounds such as ethyl acetoac-etate or 2,4-pentanedione. As only the firsttwo sugar carbons contribute to the forma-

tion of the furan, a distinctly hydrophilic tetra-hydroxylbutyl side chain is introduced intothe heterocycle.D-Glucose, e.g., smoothly andefficiently provides furans withD-arabino-configuration in the polyol fragment [139],[140], which can be shortened oxidatively to thedicarboxylic acid or a variety of other furanicbuilding blocks:

9.2.2. Pyrones and Dihydropyranones

The bulk scale-accessible mono- and disaccha-rides listed in Table 3 are preferentially adopt-ing the pyranose cyclohemiacetal forms, fromwhich efficient reaction pathways lead to an un-usually large variety of unsaturated pyranoidbuilding blocks, such as pyrones, dihydropy-rans, and dihydropyranones.

The γ-pyrone kojic acid is readily obtainedfrom D-glucose either enzymatically byAs-pergillus oryzae(growing on steamed rice)[141] or chemically via pyranoid 3,2-enolones[102], [109]. An isomericα-pyrone is producedfrom D-glucose by oxidation toD-gluconic acidand acetylation (1 h, 80◦C, 90 %) [142]. Both,at present, are of little significance as start-ing materials for preparative purposes, despitea surprisingly effective route to cyclopentanoidproducts [143] which are surmised to have in-dustrial potential.


Of higher interest, at least with respect totheir extensive use for the total synthesis ofnon carbohydrate natural products [101], [102],are the bevy of enantiopure six-carbon buildingblocks of the dihydropyran and dihydropyra-none type in Tables 4 and 5, all compounds de-picted being readily accessible fromD-glucosein no more than three to five straightforwardsteps [102], [144].

Table 4.Enantiopure six-carbon building blocks readily accessiblein 3 – 5 straightforward steps fromD-glucose viaD-glucal ester askey intermediate (R = Ac, Bz) [107], [144] (R’ = Me, Et)

Glucal ester

Table 5.Pyranoid building blocks fromD-glucose via hydroxyglu-cal esters (R = Ac, Bz; R′ = Me, Et) [106] as key intermediates.

2-Hydroxyglucal ester 2,3-Enol esters [107]

Enol lactones [148] 2,3-Enolones [146]

Ene-diolones [147] 3,4-Enolones [148]

Some of these pyranoid building blocks areaccessible even more directly, e.g., levoglu-cosenone, which has been used for the synthesisof a diverse variety of natural products [149].Although the yield attainable from pyrolysisof waste paper [150] is low (3 – 4 %), relativelarge quantities can be amassed quickly. Simi-larly convenient are the preparations of the threeglycosylated dihydropyranones requiring two,three, and four steps from maltose, sucrose, andlactose, respectively:


Levoglucosenone4 % from waste paper [150]

58 % (2 steps)from maltose [147]

38 % (3 steps)from sucrose [27]

52 % (4 steps)from lactose [145]

Ac = acetyl; Bz = benzoyl; Pv = pivalolyl

All of these pyranoid building blocks areenantiopure, and have a unique, highly diversearray of functional groups to which the hugearsenal of preparative organic methods can beapplied directly, reflecting the extensive use ofthese building blocks in the total synthesis ofnon carbohydrate natural products in enantiop-ure form [101], [102], [149]. They have foundlittle use, though, as high-value-added specialtychemicals. However, if suitable targets and ap-propriate preparative outlets can be found, par-ticularly along pharmaceutical objectives to-wards biologically hopeful compound librariesvia combinatorial techniques, these pyranoidbuilding blocks are apt to become a plethora ofattractive, industrially relevant specialty chemi-cals.

9.2.3. Sugar-Derived UnsaturatedN-Heterocycles

Although transformation of sugars into traceamounts ofN-heterocycles occurs extensivelyon exposure of foods to heat (Maillard reaction[59]), and despite the fact that various nitro-gen heterocycles have been generated from sac-charide derivatives [151], synthetic proceduresmeeting preparative standards are exceedinglyscarce. Recent improvements of existing proce-dures and the development of new methodolo-

gies have led to the more ready access to variousN-heterocycles from carbohydrates. Examplesare imidazoles, pyrroles, pyrazoles, pyridines,and quinoxalines which due to their derivationfrom sugars have hydrophilic side chains.

Pyrroles. The formation of pyrroles by heat-ing a glycerol solution of the lactose-derivedammonium salt of galactaric acid [152] overa free flame [153] appears to be the produc-tion process from a carbohydrate source givingthe highest yield (40 %). However, this processdoes not seem to be utilized industrially, neitherin this nor in modified form.

2,5-Disubstituted pyrroles are accessi-ble from carbohydrate sources via HMF ina preparatively straightforward reaction se-quence, involving photooxidative furan ringopening and cyclization of the saturated 2,5-diketones with ammonia or amines [154]:

These reaction sequences can directly betransferred to GMF, leading to pyrroles carryingan additional glucosyl residue [154]. Pyrroleswith an equally hydrophilic tetrahydroxybutylsubstituent are available fromD-glucosamine


by exposure to acetylactone or ethyl acetoac-etate under mildly basic conditions [155] or ina one-pot reaction fromD-fructose by heatingwith acetylacetone and ammonium carbonate inDMSO [156].

The hydroxylated side chain can, of course,be oxidatively shortened to give a variety ofsimple pyrrole building blocks, cyclized to a fu-ranoid ring. These compounds may be consid-ered asC-nucleosides [155].

Pyrazoles.An expeditious four-step ap-proach to 1-phenylpyrazol-3-carboxaldehydeswith a 5-hydroxymethyl, 5-dihydroxyethyl, or a5-glucosyloxymethyl substituent has been elab-orated starting fromD-xylose [157],D-glucose,and isomaltulose [158], respectively.

The osazone ofD-xylose, nearly quan-titatively formed on reaction with phenyl-hydrazine, straightforwardly cyclizes to thepyrazole upon addition to refluxing acetic

anhydride. Subsequent removal of theN-acetylphenylhydrazone residue with formalde-hyde/acetic acid and de-O-acetylation pro-vides a pyrazole-aldehyde (57 % overall yieldfrom D-xylose), a versatile heterocyclic build-ing block, useful in the synthesis of pharma-ceuticals or monomers for the production ofpolyamides and polyesters, e.g., in the form ofits the diamino and diol derivatives [157]:

Imidazoles.Various imidazoles carryinghydrophilic substituents in the 4-position arereadily accessible in one-pot procedures fromthe standard monosaccharides. Of those, theformation of 4-hydroxymethylimidazole byCu(II)-promoted reaction of monosaccharideswith formaldehyde and conc. ammonia [159] israther unique, because obviously retroaldoliza-tion to glyceraldehyde and dihydroxyacetone isinvolved. The retroaldol fission can be partiallysuppressed when heating a monosaccharide,D-fructose for instance, with formamidiniumacetate in liquid ammonia in a pressure ves-sel [160], or with formamidinium acetate inthe presence of boric acid and hydrazine [161].The latter reaction obviously proceeds via aboric acid complex of the bishydrazone ofD-glucosone (2-ketoglucose).

ConditionsA CH2O, aq. NH3, CuCO3/Cu(OH)2, 2 h, 100◦C, [158]B HC(NH)NH2 · HOAc/liq. NH3, 15 h, 75◦C, [159]C N2H4/HC(NH)NH2 · HOAc/aq. HOAc, H3BO3, 3 h

reflux, [160]

These conditions can be readily applied topentoses or disaccharides, as exemplified withD-xylose [160] and isomaltulose [161] in forone-pot procedures acceptable yields:


3-Pyridinols. The conversion of pentosansor pentoses into 3-pyridinol can be effected ina practical three-step sequence, involving acid-induced dehydration to furfural, reductive ami-nation to furfurylamine, and subsequent oxida-tion wit hydrogen peroxide [134], [162], the laststep conceivably proceeding through the stageof a 2,5-dihydroxy-2,5-dihydrofurfurylamine,which gives the pyridine nucleus via dehydra-tion to a 5-aminopentenal intermediate and in-tramolecular aldimine formation. The pyridinolis an important intermediate in the preparationof herbicides and insecticides [163] as well ascholinergic drugs of the pyridostigmine type.

For the conversion of furfurylamines withoxidizable hydroxyl groups, e.g., those derivedfrom fructose via HMF, the multistep process tothe hydroxymethyl-pyridinol can be effected ina one-pot procedure simply by treatment withbromine in water-methanol at 0◦C [164]:

Quinoxalines.Useful one-pot proceduresare also available for the conversion of variousmonosaccharides into tetrahydroxybutyl substi-tuted quinoxalines, the preparatively most fa-vorable conditions seem to be reaction of fruc-tose with hydrazine,o-phenylenediamine andboric acid in dilute acetic acid with bubblingoxygen through the solution [165], the deci-sive intermediate being the bishydrazone ofD-glucosone:


R = H (45 %) [166], R = Ph (90 %) [167]On briefly refluxing the quinoxaline in aque-

ous acid with excess hydrazine or phenylhy-drazine, a surprising oxidative cyclization takesplace to form the trihydroxypropyl-substitutedflavazols [166], [167].

9.2.4. Sugar-Based Surfactants

Utilization of cheap, bulk-scale accessible sug-ars as the hydrophilic component and fattyacids or fatty alcohol as the lipophilic partprovides nonionic surfactants which are non-toxic, nonskin-irritating and fully biodegrad-able. The industrially relevant surfactants alongthis route are fatty acid esters of sorbitol andsucrose, fatty acid amides of 1-methylami-

no-1-deoxy-D-glucitol, and, most pronouncedin terms of volume produced, fatty alcoholglucosides, the so-called alkyl polyglucosides(→Surfactants, Chap. 7.4.;→Laundry Deter-gents, Chap. 3.1.2.6.).

Fatty Acid Esters of Sorbitol (SorbitanEsters).Sorbitol, well accessible by catalytichydrogenation ofD-glucose (see Table 3), read-ily undergoes dehydration to “sorbitan” whichconstitutes a mixture of sorbitol, its 1,4-anhydroand 1,4:3,6-dianhydro derivatives, the exactcomposition depending on the conditions em-ployed, usually acid catalysis. Esterification ofthis mixture is generally carried out with fattyacids or their methyl esters at 200 – 250◦Cwith 0.1 N NaOH. Depending on the amountof fatty acids used, sorbitan monoester (‘SMS’,R = C16/C18 acyl), di- or triester (“SMT”) areformed:

SMS is dispersible in water and soluble infats and oils and has low hydrophilic lipophilicbalance (HLB) values, besides as a surfactantSMS finds use as an emulsifier in desserts [168].

Sucrose Fatty Acid Esters.Surfactantsbased on sucrose have gained limited accep-


tance industrially due to the instability of itsintersaccharidic bond, and its insolubility inconventional organic solvents. This requiresthe use of the rather toxic and expensive di-methylformamide or dimethylsulfoxide for ef-fecting transesterification with fatty acid methylesters and complete removal of the solvents. Al-ternately, transesterification of fats with sucrosewithout a solvent is also possible. In either case,the resulting sucrose monoester (if 1:1 molar ra-tios have been used in the esterification process)is not a defined product acylated exclusively atthe primary glucose-6-OH, as indicated in theformula, but at the other primary and some ofthe secondary OH groups as well:

Sucrose fatty acid monoesters, presently pro-duced at a 4000 t/a only, are mostly used in thefood industry as emulsifiers and in cosmetic for-mulations because of their attractive physiolog-ical properties.

Whilst sucrose fatty acid mono- or diestersare biodegradable, fully or nearly completelyesterified analogs (octa- or heptaesters) are not.The sucrose molecule is fully encased in a man-tle of long-chain alkyl groups, so that enzymeshave no way of binding to the sugar, whichis a prerequisite for degradation. Thus, Olestra[169], a sucrose fatty acid hepta-/octaester,which has the consistency of an oil or a soliddepending on the nature of fatty acid used, canbe used as a noncaloric fat (‘fat-free fat’ [170])in food applications including frying, due to itsthermal stability.

N-Methyl-N-acyl-glucamides (NMGA).Reductive amination ofD-glucose with methy-lamine smoothly generates the respective ami-noalditol, 1-methylamino-1-deoxy-D-glucitol,which on amidation with fatty acids givesthe corresponding fatty acid amides, carrying

a methyl group and a pentahydroxylated six-carbon chain at the amido nitrogen.

The NMGA’s possess highly advantageousecological and toxicological properties whichbrought about their use as surfactants, cleansingagents and cosmetic applications [171], [172](→Laundry Detergents, Chap. 3.1.2.5.).

Alkylpolyglucosides (APG) [173].Presently produced in two plants with a ca-pacity of up to 40 000 t/a each, APG’s are byfar the most important nonionic surfactants.Alkylpolyglucosides are fatty alcohol gluco-sides with an alcohol chain length normallybetween C8 and C14. Their industrial synthesiseither comprises a direct acid-catalyzed Fis-cher glycosidation of glucose (in the form of asyrupy starch hydrolysate) or starch itself. Thealternate process consists of two stages, the firstbeing Fischer glycosidation withn-butanol tobutyl glycosides which are subsequently sub-jected to acid-promoted transacetalization:


APG’s are not skin-irritating, have goodfoaming properties, and are readily biodegrad-able, hence are widely used in manual dish-washing detergents and in formulations ofshampoos, hair conditioners, and other personalcare products.

9.2.5. Hydrophilic Monomers of Polyamides

Polyamide production worldwide amounted toabout 5.8×106 t in 1998 [174]. More than90 % of these polyamides are based on six-carbon monomers, i.e., caprolactam (nylon 6),and adipic acid/hexamethylenediamine (nylon66).

Nylon 6

Nylon 66

As six-carbon compounds in the form ofhexoses are abundantly available in nature,substantial efforts have been made to derivemonomers suitable for polyamidation from thebulk scale-accessible hexoses. This approachbecomes particularly evident, when consideringthe large variety of amincarboxylic acids, dicar-boxylic acids, and diamines (Table 6), that areaccessible from the common six-carbon sugars[175], [176].

Table 6. Sugar-derived six-carbon building blocks suitable forpolyamidation [175], [176]

D-Glucaric acid (Glucose)

D-Galactaric acid (Lactose)

Furan-2,5-dicarboxylicacid

(Fructose)

1,6-Diamino-1,6-dideoxy-D-glucitol

(Glucose)

2,5-Diamino-1,4:3,6-dianhydro-sorbitol

(Glucose)

2,5-Bis(ami-nomethyl)furan

(Fructose)

6-Amino-D-gluconic acidlactam (R = H, CH3)

(Glucose)

Of the myriad of possible combinationsof these sugar-derived monomers either withthemselves or with the common, petrochemi-cally derived diamines and dicarboxylic acids,an immense number have been realized. Inthe following only a few of the respectivepolyamides are exemplarily covered.

Solution or interfacial polycondensation ofgalactaric acid dichloride in its acetylated formwith various aliphatic and aromatic diamines re-sulted in a series of polyamides [175], [177], theone resulting from 1,6-diaminohexane resem-bling a nylon-6,6 in which half of the hydro-gens of the methylene chain have been substi-tuted by acetoxy groups (R = Ac). These can bedeacylated with aqueous ammonia to give thetetra-hydroxylated nylon 66:


In the case ofD-glucaric acid, the use ofits 3,6-lactone monomethyl ester proved ad-vantageous to generate stereoregular polyglu-caramides, effected with an impressive array ofaliphatic and aromatic diamines [178]:

Sugar-based “quasi-aromatic” monomers forpolyamides, i.e., the furan-2,5-dicarboxylicacid, appear particularly relevant as they em-body the potential to replace petrochemicallyderived terephthalic or isophthalic acid in thepresent industrial products. Similar potentialpertains to the furanic 1,6-diamine as a sub-stitute for p-phenylenediamine. Indeed, a se-ries of such furanic polyamides has been pre-pared [179] using the furan dicarboxylic acidand aliphatic as well as aromatic diamines. Ofthese, the polyamide resulting from conden-sation of furan-2,5-dicarboxylic acid withp-phenylenediamine, an analog of Nomex andKevlar, has particularly promising decomposi-tion and glass temperature parameters [180],

distinctly better than those found for the all-furanic polyamide:

Nomex

Kevlar

In spite of the impressive array of highly use-ful products – with respect to their applica-tion profiles they compare on the market favor-ably with the well-known polyamides – noneof these sugar-derived polyamides is, at present,produced on an industrial scale. The reasons arepurely economic because the products derivedfrom fossil raw materials are still cheaper by afactor of 5 on the average. Eventually though,with the end of cheap oil being prognosticatedfor 2040 at the latest [116], and the increasingpressure on the environment, this at present un-toward situation for products from carbohydratefeedstocks will be changing.

10. References1. J. Lehmann:Kohlenhydrate, Chemie und

Biologie, Thieme, Stuttgart/New York, 1996,372 pp.;Carbohydrates, Chemistry andBiology, Thieme, Stuttgart/New York, 1998,274 pp.

2. T. K. Lindhorst:Essentials of CarbohydrateChemistry and Biochemistry,Wiley-VCH,Weinheim, 2000, 217 pp.

3. R. V. Stick:Carbohydrates: The SweetMolecules of Life,Acad. Press, San Diego,2001, 256 pp.

4. P. M. Collins, R. J. Ferrier:Monosaccharides,their Chemistry and their Roles in Natural


Products,Wiley, Chichester/New York, 1995,574 pp.

5. J. F. Kennedy (ed.):Carbohydrate Chemistry,Clarendon Press, Oxford, 1988, 678 pp.

6. G.-J. Boons (ed.):Carbohydrate Chemistry,Blackie Academic, London/Weinheim, 1998,508 pp.

7. J. F. Robyt:Essentials of CarbohydrateChemistry,Springer, Heidelberg–New York,1998, 399 pp.

8. B. Ernst, G. W. Hart, P. Sinay (eds.):Carbohydrates in Chemistry and Biology,Vol.1-4.Wiley-VCH, Weinheim, 2000, 2340 pp.

9. B. Fraser-Reid, K. Tatsuta, J. Thiem (eds.):Glycoscience, Chemistry and ChemicalBiology, Vol. I-III, Springer, Heidelberg,2001, 2850 pp.

10. E. Fischer, “Ueber die Configuration desTraubenzuckers und seiner Isomeren,Ber.Dtsch. Chem. Ges.24 (1891) 2683 – 2687.

11. F. W. Lichtenthaler, “Emil Fischer’s Proof ofthe Configuration of Sugars: A CentennialTribute,” Angew. Chem.104(1992)1577-1593;Angew. Chem. Int. Ed. Engl.31(1992) 1541 – 1556.

12. J. M. Bijvoet, A. F. Peerdemann, A. J. vanBommel, “Determination of the AbsoluteConfiguration of Optically Active Compoundsby Means of X-Rays.Nature 168(1951)271 – 272.

13. W. N. Haworth:The Constitution of Sugars,Arnold, London, 1929, 104 pp.

14. J. A. Mills, “The Stereochemistry of CyclicDerivatives of Carbohydrates,”Adv.Carbohydr. Chem.10 (1955) 1 – 53.

15. IUPAC-IUB Joint Commission (JCBN),“Conformational Nomenclature for five- andsix-membered Ring Forms ofMonosaccharides and their Derivatives,”PureAppl. Chem.53 (1981) 1901 – 1905;Carbohydr. Res.297(1997) 20 – 23.

16. J. A. Kanters, G. Roelofsen, B. P. Alblas, I.Meinders, “The Crystal Structure ofβ-D-Fructose with Emphasis on the AnomericEffect,” Acta Cryst.B33 (1977) 665 – 672.

17. B. Schneider, F. W. Lichtenthaler, G. Steinle,H. Schiweck, “Distribution of Furanoid andPyranoid Tautomers of D-Fructose inDimethylsulfoxide, Water and Pyridine viaAnomeric Hydroxyl Proton NMR Intensitites,”Liebigs Ann. Chem.(1985) 2454 – 2464.

18. G. M. Brown, H. A. Levy, “Sucrose: PreciseDetermination of Crystal and MolecularStructure by Neutron Diffraction,”Science

141(1963) 921 – 923;Acta Cryst.B29 (1973)790 – 797.

19. J. C. Hanson, L. C. Sieker, L. H. Jensen,“Sucrose: X-Ray Refinement and Comparisonwith Neutron Refinement,”Acta Crystallogr.B29 (1973) 797 – 808.

20. R. R. Watson, N. S. Orenstein, “Chemistry andBiochemistry of Apiose,”Adv. Carbohydr.Chem. Biochem.31 (1975) 135 – 184.

21. J. Yoshimura, “Synthesis of Branched-chainSugars,”Adv. Carbohydr. Chem. Biochem.42(1984) 69 – 134.

22. A. Liptak, P. Fugedi, Z. Szurmai, J. Harangi:Handbook of Oligosaccharides, Vol. I(Disaccharides, 474 pp.), Vol. II(Trisaccharides, 267 pp.), Vol. III (HigherOligosaccharides, 179 pp.), CRC Press, BocaRaton/Boston, 1990.

23. A. Hugill: Introductory DedicationalMetaphor to Sugar and All That. A History ofTate & Lyle, Gentry Books, London, 1978.

24. International Sugar Organization, “WorldSugar Production 2000/2001,”Zuckerind.(Berlin) 126(2001) 300, 577.

25. S. Immel, F. W. Lichtenthaler, “TheConformation of Sucrose in Water: AMolecular Dynamics Approach,”Liebigs Ann.Chem.(1995) 1925 – 1937.

26. H. Schiweck, M. Munir, K. M. Rapp, B.Schneider, M. Vogel, “Use of Sucrose as anIndustrial Bulk Chemical and Production ofIsomaltulose and Isomalt,”Zuckerind. (Berlin)115(1990) 555 – 565.

27. F. W. Lichtenthaler, P. Pokinskyj, S. Immel,“Sucrose as a Renewable Raw Material. NewReactions via Computer Simulation ofHydroxyl Group Reactivities,”Zuckerind.(Berlin) 121(1996) 174 – 190.

28. A. Varki, “Biological Roles ofOligosaccharides,”Glycobiology 3 (1993)97 – 130.

29. H. M. I. Osborn, T. H. Khan:Oligosaccharides. Their Synthesis andBiological Roles,Oxford University Press,Oxford, 2000, 112 pp.

30. H.-J. Gabius, S. Gabius (eds.):Glycosciences–Status and Perspectives,Chapman & Hall, London/Weinheim, 1997,631 pp.

31. J. Kopitz: “Glycolipids: Structure andFunction,” in [30], pp 163 – 189.

32. N. Sharon, H. Lis: “Glycoproteins: Structureand Function,” in [30], pp 133 – 162.


33. J. Szejtli, “Introduction and General Overviewof Cyclodextrin Chemistry,”Chem. Rev.98(1998) 1743 – 1753.

34. F. W. Lichtenthaler, S. Immel, “TowardsUnderstanding Formation and Stability ofCyclodextrin Inclusion Complexes.Visualization of their Lipophilicity Patterns,”Starch/Starke 48 (1996) 145 – 154.

35. All 3D-structures can be viewed on the wwwat: http://caramel.oc.chemie.tu-darmstadt.de/immel/3Dstructures.html;MOLCAD graphics are available at:http://caramel.oc.chemie.tu-darmstadt.de/immel/molcad/gallery.html.

36. J. Szejtli, “Medical Applications ofCyclodextrins,”Med. Res. Rev.14 (1994)353 – 386.

37. J. K. Uekama, F. Hitayama, T. Ivie,“Cyclodextrin Drug Carrier Systems,”Chem.Rev. 98 (1998) 2045 – 2076.

38. V. Schurig, H. P. Novotny,“Gaschromatographic Separation ofEnantiomers on Cyclodextrin Derivatives,”Angew. Chem.102(1990) 969 – 986;Angew.Chem. Int. Ed. Engl.29 (1990) 939 – 958.

39. S. Li, W. C. Purdy, “Cyclodextrins and theirApplications in Analytical Chemistry,”Chem.Rev. 92 (1992) 1457 – 1470.

40. G. Wenz, “Cyclodextrins as Building Blocksfor Supramolecular Structures and FunctionalUnits,” Angew. Chem.106(1994) 851 – 870;Angew. Chem. Int. Ed. Engl.33 (1994)803 – 822.

41. I. Tabushi, “Design Synthesis of ArtificialEnzymes,”Tetrahedron40 (1984) 269 – 292.

42. T. L. Bluhm, P. Zugenmaier, “DetailedStructure of the VH-amylose-Iodine Complex:A linear polyiodide chain,”Carbohydr. Res.89 (1981) 1 – 10.

43. S. Immel, F. W. Lichtenthaler, “TheHydrophobic Topographies of Amylose and itsBlue Iodine Complex,”Starch/Starke 52(2000) 1 – 8.

44. A. Fuchs (ed.):Inulin and Inulin-containingCrops, Elsevier, Amsterdam/New York, 1993,417 pp.

45. A. Fuchs, “Potentials for Non-food Utilizationof Fructose and Inulin,”Starch/Starke 39(1987) 335 – 343.

46. J. F. Kennedy, C. A. White: “The Plant, Algaland Microbial Polysaccharides,” in J. F.Kennedy (ed.):Carbohydrate ChemistryOxford Science Publ., Oxford 1988, pp220 – 262.

47. R. J. Sturgeon: “The Glycoproteins andGlycogen,” in J. F. Kennedy (ed.):Carbohydrate ChemistryOxford SciencePubl., Oxford, 1988, pp 263 – 302.

48. IUPAC-IUB Joint Commission,“Nomenclature of Carbohydrates (1996Recommendations),”Pure Appl. Chem.68(1996) 1919 – 2008, orCarbohydr. Res.297(1997) 1 – 92, orAdv. Carbohydr. Chem.Biochem.52 (1997) 47 – 177.

49. J. Szejtli:Saurehydrolyse glycosidischerBindungen. Einfluß von Struktur undReaktionsbedingungen auf die Saurespaltungvon Glykosiden, Disacchariden, Oligo- undPolysacchariden,VEB Fachbuchverlag,Leipzig 1976, 399 pp.

50. C. J. Biermann, “Hydrolysis and OtherCleavages of Glycosidic Linkages inPolysaccharides,”Adv. Carbohydr. Chem.Biochem.46 (1988) 251 – 271.

51. O. Theander, D. A. Nelson, “Aqueous,High-Temperature Transformation ofCarbohydrates towards Biomass Utilization,”Adv. Carbohydr. Chem. Biochem.46 (1988)273 – 332.

52. W. J. McKillip, “Furan and Derivatives,”Kirk-Othmer Encyclopedia ChemicalTechnology,11 (1981) 501 – 527.

53. B. F. M. Kuster, “Manufacture of5-Hydroxymethylfurfural,”Starch/Starke 42(1990) 314 – 312.

54. D. Martin, T. Weber, H. Schiweck,“5–(α-D-Glucosyloxymethyl)-furfural:Preparation from Isomaltulose andExploration of its Ensuing Chemistry”,Liebigs Ann. Chem.(1993) 967 – 974.

55. S. J. Angyal, “The Lobry de Bruyn-Alberdavan Ekenstein Transformation and RelatedReactions,”Topics Current Chem.215(2001)1 – 14.

56. JP 73-49938, 1971 (I. Machida, J. Kanaeda, H.Miki, S. Kubomura, H. Toda, T. Shirioshi).Chem. Abstr.79 (1973) 126744v.

57. F. W. Lichtenthaler, S. Ronninger,“α-D-Glucopyranosyl-D-fructoses.Distribution of Furanoid and PyranoidTautomers in Water, DMSO and Pyridine,”J.Chem. Soc. Perkin Trans. 2(1990)1489 – 1497.

58. L. Petrus, M. Petrusova, Z. Hricoviniova, “TheBılik Reaction,”Topics Current Chem.215(2001) 16 – 41.

59. F. Ledl, E. Schleicher, “Die Maillard-Reaktionin Lebensmitteln und im menschlichenKorper,”Angew. Chem.102(1990) 597 – 626;


Angew. Chem. Int. Ed. Engl.29 (1990)565 – 594.

60. A. F. Bochkov, G. E. Zaikov:The Chemistry ofthe O-Glycosidic Bond,Pergamon Press,Oxford, 1979, 210 pp.

61. T. Ziegler: “Protecting Group Strategies forCarbohydrates,” in G.-J. Boons (ed.):Carbohydrate Chemistry,Blackie Academic,London/Weinheim, 1998, pp 21 – 45.

62. M. Nitz, D. R. Bundle: “Glycosyl Halides inOligosaccharide Synthesis,” in B. Fraser-Reid,K. Tatsuta, J. Thiem (eds.):GlycoscienceVol.II, 2002, pp 1497 – 1544.

63. F. W. Lichtenthaler, E. Kaji, T.Schneider-Adams, “2-Oxo- and2-Oximino-glycosyl Halides. VersatileGlycosyl Donors for the Construction ofβ-D-Mannose- andβ-D-Mannosamine-containingOligosaccharides,”Trends Glycosci.Glycotechnol.5 (1993) 121 – 142;J. Org.Chem.59 (1994) 6728-6734 and 6735 – 6738;Carbohydr. Res.305(1998) 293 – 303.

64. M. Nitz, D. R. Bundle, “Synthesis of Di- toHexasaccharide 1,2-Linkedβ-MannopyrananOligomers and a Terminal S-LinkedTetrasaccharide Congener,”J. Org. Chem.66(2001) 8411 – 8423.

65. E. R. Palmacci, O. J. Plante, P. H. Seeberger,“Oligosaccharide Synthesis in Solution and onSolid Support with Glycosyl Phosphates,”Eur.J. Org. Chem.(2002) 595 – 606.

66. R. R. Schmidt, W. Kinzy, “Anomeric-oxygenActivation for Glycoside Synthesis: TheTrichloroacetimidate Method,”Adv.Carbohydr. Chem. Biochem.50 (1994)21 – 124.

67. P. J. Garegg, “Thioglycosides as GlycosylDonors in Oligosaccharide Synthesis,”Adv.Carbohydr. Chem. Biochem.52 (1997)179 – 205.

68. L. Yan, D. Kahne, “GeneralizingGlycosylation. Synthesis of Blood GroupAntigens Lea, Leb, and Lex,” J. Am. Chem.Soc. 118(1996) 9239 – 9248.

69. S. J. Danishefsky, M. T. Bilodean, “Glycals inOrganic Synthesis. Comprehensive Strategiesfor the Assembly of Oligosaccharides,”Angew.Chem.108(1996) 1482 – 1522;Angew.Chem. Int. Ed. Engl.35 (1996) 1380 – 1419.

70. K. Fucase: “Combinatorial and Solid PhaseMethods in Oligosaccharide Syntheses,” in B.Fraser-Reid, K. Tatsuta, J. Thiem (eds.):Glycoscience,Vol. II Springer,Heidelberg – New York, 2001, pp 1661 – 1694.

71. G.-J. Boons: “Strategies and Tactics inOligosaccharide Synthesis,” in G.-J. Boons(ed.):Carbohydrate ChemistryBlackieAcademic, London/Weinheim, 1998, pp.175 – 222.

72. Ref. [8], Vol. 1, pp 1 – 583.73. G. Magnusson, U. J. Nilson: “Regio- and

Stereoselective Methods of Glycosylation,” inB. Fraser-Reid, K. Tatsuta, J. Thiem (eds.):Glycoscience,Vol. II Springer,Heidelberg – New York, 2001, pp 1543 – 1588.

74. J. D. Wander, D. Horton, “Dithioacetals ofSugars,”Adv. Carbohydr. Chem. Biochem.32(1976) 15 – 123.

75. T. J. Wrodnigg, B. Eder, “The Amadori andHeyns Rearrangements,”Topics Curr. Chem.215(2001) 115 – 152.

76. H. S. El Khadem, A. F. Fatiadi, “HydrazineDerivatives of Carbohydrates and RelatedCompounds,”Adv. Carbohydr. Chem.Biochem.55 (1999) 175 – 263.

77. C. S. Hudson, “The Kiliani-FischerCyanohydrin Synthesis,”Adv. Carbohydr.Chem.1 (1945) 1 – 36.

78. J. C. Sowden, “The Nitromethane and2-Nitroethanol Syntheses,”Adv. Carbohydr.Chem.6 (1951) 291 – 318.

79. F. L. Humoller, “β-D-Allose,” MethodsCarbohydr. Chem.1 (1962) 102 – 104.

80. J. C. Sowden, “L-Glucose and L-Mannose,”Methods Carbohydr. Chem.1 (1962)132 – 135.

81. F. W. Lichtenthaler, “Cyclizations ofDialdehydes with Nitromethane,”Angew.Chem.76 (1964) 84-97;Angew. Chem. Int.Ed. Engl. 3 (1964) 135 – 148.

82. H. H. Baer, “The Nitro Sugars,”Adv.Carbohydr. Chem. Biochem.24 (1969)67 – 138.

83. F. W. Lichtenthaler, “Amino Sugars andAmino Cyclitols via Cyclization ofDialdehydes with Nitromethane,”MethodsCarbohydr. Chem.6 (1972) 250 – 260.

84. F. W. Lichtenthaler, “Branched-chain AminoSugars viaDialdehyde-Nitroalkane-Cyclization,”Fortschr. Chem. Forschg.14 (1970) 556 – 577.

85. D. L. MacDonald, H. O. L. Fischer, “TheDegradation of Sugars by Means of theirDisulfones,”J. Am. Chem. Soc.74 (1952)2087 – 2090.

86. P. J. Sicard: “Hydrogenated Glucose Syrups,Sorbitol, Mannitol and Xylitol,” in G. G.Birch, K. J. Parker (eds.):Nutritive Sweeteners


Applied Science Publ., London/New Jersey,1982, pp 145 – 170.

87. C. K. Lee, “The Chemistry and Biochemistryof the Sweetness of Sugars,”Adv. Carbohydr.Chem. Biochem.45 (1990) 199 – 351.

88. P. J. Sicard, P. Leroy: “Mannitol, Sorbitol andLycasin; Properties and Food Applications,” inT. H. Grenby, K. J. Parker, M. G. Lindley,(eds.):Developments in Sweeteners-2Appl.Science Publ., London – New York, 1983, pp1 – 26.

89. H. J. Lindner, F. W. Lichtenthaler, “ExtendedZig-zag Conformation of1-O-α-D-Glucopyranosyl-D-mannitol,”Carbohydr. Res.93 (1981) 135 – 140.

90. C. L. Mehltretter, “D-Glucaric Acid,”MethodsCarbohydr. Chem.2 (1963) 46 – 48.

91. H. E. Conrad, “Methylation of Carbohydrateswith Methylsulfinyl Anion and Methyl Iodidein DMSO,” Methods Carbohydr. Chem.6(1972) 361 – 364.

92. C. M. McCloskey, “Benzyl Ethers of Sugars,”Adv. Carbohydr. Chem.12 (1957) 137 – 156.

93. C. C. Sweely, R. Bentley, M. Makita, W. W.Wells, “Gas-Liquid-Chromatography ofTrimethylsilyl Derivatives of Sugars,”J. Am.Chem. Soc.85 (1963) 2497–2507.

94. C. E. Ballou, D. L. MacDonald,“Phosporylation with DiphenylPhosphorochloridate,”Methods Carbohydr.Chem.2 (1963) 270 – 272; 273 – 276;277 – 281; 282 – 288.

95. C.-H. Wong, G. M. Whitesides:Enzymes inSynthetic Organic Chemistry,ElsevierScience, Oxford, 1994.

96. R. L. Whistler, W. W. Spencer, J. N. BeMiller,“Sulfates,”Methods Carbohydr. Chem.2(1963) 298 – 303.

97. J. Honeyman, J. W. W. Morgan, “SugarNitrates,”Adv. Carbohydr. Chem.12 (1957)117 – 135.

98. F. W. Lichtenthaler, H. J. Muller, “Preparationof Nucleoside 5’-Nitrates,”Synthesis(1974)199 – 201.

99. L. A. Silvieri, N. J. DeAngelis: In K. Florey(ed.):Profiles of Drug Substances,Vol. 4,Acad. Press, New York, pp 225 – 244.

100. K. Igarashi, “The Koenigs-Knorr Reaction,”Adv. Carbohydr. Chem. Biochem.34 (1977)243 – 283.

101. S. Hanessian:Total Synthesis of NaturalProducts: The Chiron Approach,Pergamon,Oxford/New York, 1983.

102. F. W. Lichtenthaler: “Building Blocks fromSugars and their Use in Natural Product

Synthesis. A Review with Procedures.” in R.Scheffold (ed.):Modern Synthetic Methods,Vol. 6, VCH Verlagsgesellschaft, Weinheim,1992, pp 273 – 376.

103. G. J. Boons, K. J. Hale:Organic Synthesiswith Carbohydrates,Sheffield Acad. Press,Sheffield, 2000, 336 pp.

104. E. Fischer, “Ueber neue Reduktionsproduktedes Traubenzuckers: Glucal und Hydroglucal,”Ber. Dtsch. Chem. Ges.47 (1914) 196 – 210;Methods Carbohydr. Chem.2 (1963)405 – 408.

105. L. Somsak, I. Nemeth, “A Simple Method forthe Synthesis of Acylated Pyranoid Glycalsunder Aprotic Conditions,”J. Carbohydr.Chem.12 (1993) 679 – 684.

106. M. G. Blair, “The 2-Hydroxyglycals,”Adv.Carbohydr. Chem.9 (1954) 97 – 130;MethodsCarbohydr. Chem.2 (1963) 411 – 414.

107. R. J. Ferrier, “Modified Synthesis of(2-Hydroxylglycal) Esters,”MethodsCarbohydr. Chem.6 (1972) 307 – 311.

108. N. L. Holder, “The Chemistry of Hexuloses,”Chem. Rev.82 (1982) 287 – 33.

109. F. W. Lichtenthaler, “SugarEnolones–Synthesis, Reactions of PreparativeInterest, andγ-Pyrone Formation,”Pure Appl.Chem.50 (1978) 1343 – 1362.

110. F. W. Lichtenthaler, U. Klares, M.Lergenmuller, S. Schwidetzky, “GlycosylDonors with a Keto or Oximino Function nextto the Anomeric Centre: Practical Preparationand Evaluation of their Selectivites inGlycosidation,”Synthesis(1992) 179 – 184.

111. F. W. Lichtenthaler, T. Schneider-Adams,“3,4,6-Tri-O-benzyl-α-D-arabino-hexopyranos-2-ulosyl Bromide–a GlycosylDonor for the Efficient Generation ofβ-D-Mannosidic Linkages,”J. Org. Chem.59(1994) 6728 – 6734.

112. F. W. Lichtenthaler, T. Schneider-Adams, S.Immel, “A Practical Synthesis ofβ-D-Xyl-(1→2)-β-D-Man-(1→4)-D-GlcOMe, aTrisaccharide Component of theGlycosphingolipid of Hyriopsis schlegelii,”J.Org. Chem.59 (1994) 6735 – 6738.

113. R. F. Brady, “Cyclic Acetals of Ketoses,”Adv.Carbohydr. Chem. Biochem.26 (1971)197 – 278.

114. A. N. deBelder, “Cyclic Acetals of theAldoses and Aldosides,”Adv. Carbohydr.Chem. Biochem.34 (1977) 179 – 241.

115. D. M. Clode, “Carbohydrate Cyclic AcetalFormation and Migration,”Chem. Rev.79(1979) 491 – 513.


116. C. J. Campbell, J. H. Laherrere, “The End ofCheap Oil,”Sci. Am.1998, March, 60 – 65.

117. D. H. Klass: “Fossil Fuel Reserves andDepletion,”Biomass for Renewable Energy,Fuels and Chemicals,Acad. Press, SanDiego, 1998, pp 10 – 19.

118. C. Okkerse, H. van Bekkum, “Fossil toGreen,”Green Chem.(1999) 107 – 114.

119. National Research Council, USA. BiobasedIndustrial Products: Priorities for Research andCommercialization, Natl. Acad. Press,Washington, 2000.

120. D. L. Klass: “Organic Commodity Chemicalsfrom Biomass,” inBiomass for RenewableEnergy, Fuels and Chemicals,Acad. Press,San Diego, 1998, pp 495 – 546.

121. F. W. Lichtenthaler:Carbohydrates asOrganic Raw Materials,VCHVerlagsgesellschaft, Weinheim, 1991, 350 pp.

122. G. Descotes:Carbohydrates as Organic RawMaterials II, VCH Verlagsgesellschaft,Weinheim, 1993, 270 pp.

123. M. Eggersdorfer, S. Warwel, G. Wulff (eds.):Nachwachsende Rohstoffe: Perspektiven furdie Chemie,VCH Verlagsgesellschaft,Weinheim, 1993, 388 pp.

124. H. van Bekkum, H. Roper, A. Voragen:Carbohydrates as Organic Raw Materials III,VCH Verlagsgesellschaft, Weinheim, 1996,306 pp.

125. H. Eierdanz (ed.):Perspektivennachwachsender Rohstoffe in der Chemie,VCH Verlagsgesellschaft, Weinheim, 1996.

126. F. W. Lichtenthaler, S. Mondel, “Perspectivesin the Use of Low-molecular-weightCarbohydrates as Organic Raw Materials,”Pure Appl. Chem.69 (1997) 1853 – 1866.

127. F. W. Lichtenthaler, “Towards Improving theUtility of Ketoses as Organic Raw Materials,”Carbohydr. Res.313(1998) 69 – 89.

128. S. David, C. Auge, C. Gautheron, “EnzymicMethods in Preparative CarbohydrateChemistry,”Adv. Carbohydr. Chem. Biochem.49 (1991) 176 – 238.

129. A. R. Katritzky, C. W. Rees, (eds.):Comprehensive Heterocyclic Chemistry,Vol.4, Pergamon, Oxford, 1984, pp 599 – 712.

130. A. Gandini, M. N. Belgacem, “Furans inPolymer Chemistry,”Prog. Polym. Sci.22(1997) 1203 – 1279, and references therein.

131. T. El-Hajj, A. Masroua, J.-C. Martin, G.Descotes, “5-Hydroxymethylfurfural andDerivatives,”Bull. Soc. Chim. Fr.(1987)855 – 860.

132. C. Larousse, L. Rigal, A. Gaset, “ThermalDegradation of 5-Hydroxymethylfurfural,”J.Chem. Technol. Biotechnol.53 (1992)111 – 116.

133. V. Schiavo, G. Descotes, J. Mentech,“Hydrogenation of 5-Hydroxymethylfurfural,”Bull. Soc. Chim. Fr.128(1991) 704 – 711.

134. N. Elming, N. Clauson-Kaas,“6-Methyl-3-pyridinol from2-Hydroxymethyl-5-aminomethyl-furan,”ActaChem. Scand.10 (1956) 1603 – 1605.

135. DE 3.826.073, 988 (E. Leupold, M. Wiesner,M. Schlingmann, K. Rapp);Chem. Abstr.113(1990) 23678t.

136. A. Gandini, M. N. Belgacem, “FuranicPolyesters,”Progr. Polym. Sci.22 (1997)1232 – 1238.

137. M. Kunz: “5-Hydroxymethylfurfural, aPossible Basic Chemical for IndustrialIntermediates,” in A. Fuchs (ed.):Inulin andInulin-containing CropsElsevier, Amsterdam,1993, pp 149 – 160.

138. US 4 497 961 1980 (J. W. Clitherow);Chem.Abstr. 102(1985) 166604z.

139. F. Garcia-Gonzales, “Reactions ofMonosaccharides withβ-Ketoesters,”Adv.Carbohydr. Chem.11 (1956) 97 – 143.

140. A. J. Moreno-Vargas, J. Fuentes, J.Fernandez-Bolanos, I. Robina, “Synthesis ofHetarylene-carbopeptoids,”Tetrahedron Lett.42 (2001) 1283 – 1285.

141. A. Beelik, “Kojic Acid,” Adv. Carbohydr.Chem.11 (1956) 145 – 183.

142. C. Nelson, J. Gratzl, “Conversion ofD-Glucono-1,5-lactone into anα-Pyrone,”Carbohydr. Res.60 (1978) 267 – 273.

143. K. Tajima, “Cyclopentenones from3-Acetoxy-6-acetoxymethyl-2-pyrone,”Chem.Lett. (1987) 1319 – 1322.

144. M. Bols:Carbohydrate Building Blocks,Wiley, New York, 1996, 182 pp.

145. F. W. Lichtenthaler, S. Ronninger, P. Jarglis,“Expedient Approach to Pyranoid Ene andEnol Lactones,”Liebigs Ann.(1989)1153 – 1161.

146. F. W. Lichtenthaler, U. Kraska, “Preparation ofSugar Enolones,”Carbohydr. Res.58 (1977)363 – 377.

147. F. W. Lichtenthaler, S. Nishiyama, T. Weimer,“2,3-Dihydropyranones with ContiguousChiral Centers,”Liebigs Ann. Chem.(1989)1163 – 1170.

148. F. W. Lichtenthaler, S. Ogawa, P. Heidel,“Synthesis of UnsaturatedHexopyranosid-4-uloses,”Chem. Ber.110(1977) 3324 – 3332.


149. Z. J. Witczak, “Synthesis of Natural Productsfrom Levoglucosenone,”Pure Appl. Chem.66(1994) 2189 – 2192.

150. F. Shafizadeh, R. H. Furneaux, T. T.Stevenson, “Reactions of Levoglucosenone,”Carbohydr. Res.71 (1979) 169 – 191.

151. H. El Khadem, “N-Heterocycles fromSaccharide Derivatives,”Adv. Carbohydr.Chem.25 (1970) 351 – 405.

152. B. A. Lewis, F. Smith, A. M. Stephen,“Galactaric Acid,”Methods Carbohydr. Chem.2 (1963) 38 – 46.

153. S. M. McElvain, K. M. Bolliger, “Pyrrole,”Org. Synth.,Coll. Vol. 1, 1941, 473 – 474.

154. F. W. Lichtenthaler, A. Brust, E. Cuny,“Hydrophilic Pyrroles, Pyridazines andDiazepinones from D-Fructose andIsomaltulose,”Green Chemistry3 (2001)201 – 209.

155. F. Garcia-Gonzales, A. Gomes Sanchez,“Reactions of Amino Sugars withβ-Dicarbonyl Compounds,”Adv. Carbohydr.Chem.20 (1965) 303 – 355.

156. A. Rozanski, K. Bielawski, J. Boltryk, D.Bartulewicz, “Simple Synthesis of 3-Acetyl-5-(tetrahydroxybutyl)-2-methylpyrrole,”Akad.Med. Juliana Marchlewskiego Bialymstoku(1991) 35 – 36, 57 – 63;Chem. Abstr.118(1992) 22471m.

157. V. Diehl, E. Cuny, F. W. Lichtenthaler,“Conversion of D-Xylose into HydrophilicallyFunctionalized Pyrazoles,”Heterocycles48(1998) 1193 – 1201.

158. M. Oikawa, C. Muller, M. Kunz, F. W.Lichtenthaler, “Hydrophilic Pyrazoles fromSugars,”Carbohydr. Res.309(1998)269 – 279.

159. R. Weidenhagen, R. Hermann,“4-Hydroxymethylimidazole,”Ber. Dtsch.Chem. Ges.70 (1937) 570 – 583;Org. Synth.,Coll. Vol. III, (1955) 460 – 462.

160. J. Streith, A. Boiron, A. Frankowski, D. LeNouen, H. Rudyk, T. Tschamber, “One-PotSynthesis of Imidazolosugars,”Synthesis(1995) 944 – 946.

161. S. Rapp, F. W. Lichtenthaler: unpublished.162. GB 862 581, 1961 (N. Elming, S. V. Carlsten,

B. Lennart, I. Ohlsson);Chem. Abstr.56(1962) 11574g.

163. EP. 227045, EP 227046, 1987(V. Koch, L.Willms, A. Fuß, K. Bauer, K. H. Bieringer, H.Buerstell);Chem. Abstr.107(1987) 175892,134217.

164. C. Muller, V. Diehl, F. W. Lichtenthaler,“3-Pyridinols from Fructose and

Isomaltulose,”Tetrahedron54 (1998)10703 – 10712.

165. H. Ohle, M. Hielscher, “Darstellung vonTetraoxybutyl-chinoxalin,”Ber. Dtsch. Chem.Ges. 74 (1941) 13 – 19.

166. H. Ohle, G. A. Melkonian, “Flavazol, einneuer Heterocyclus aus Zuckern,”Ber. Dtsch.Chem. Ges.74 (1941) 279 – 285.

167. H. Ohle, A. Iltgen, “Flavazole,”Ber. Dtsch.Chem. Ges.76 (1943) 1 – 14.

168. N. J. Krog in K. Larsson, S. E. Friberg, (eds.):Food EmulsionsMarcel Dekker, NewYork/Basel, 1990.

169. Procter & Gamble Co., US 3 600 168, 1968 (F.H. Mattson, R. A. Volpenhein);Chem. Abstr.75 (1971) 139614v.

170. “Fat-free Fat,” (Cover Story)Time Magazine(1996) Jan. 8.

171. H. Kelkenberg, “Sugar-based Detergents. NewComponents for Cleaning Compositions andCosmetics,”Tensides, Surfactants, Detergents25 (1988) 8 – 13.

172. P. Jurges, A. Turowski: “VergleichendeUntersuchung von Zuckerestern,N-Methylglucamiden und Glycosiden amBeispiel von Reinigungsprodukten,” in H.Eierdanz (ed.):Perspektiven nachwachsenderRohstoffe in der ChemieVCH Publ.,Weinheim, 1996, pp 61 – 70.

173. W. von Rybinski, K. Hill, “AlkylPolyglycosides–Properties and Applications ofa New Class of Surfactants,”Angew. Chem.110(1998) 1394 – 1412;Angew. Chem. Int.Ed. 37 (1998) 1328 – 1345.

174. H.-P. Weiß, W. Sauerer, “Polyamides,”Kunststoffe89 (1999) 68 – 74.

175. J. Thiem, F. Bachmann,“Carbohydrate-derived Polyamides,”TrendsPolym. Sci.2 (1994) 425 – 432.

176. O. Varela, H. A. Orgueira, “Synthesis ofChiral Polyamides from Carbohydrate-derivedMonomers,”Adv. Carbohydr. Chem. Biochem.55 (1999) 137 – 174.

177. E. M. E. Mansur, S. H. Kandil, H. H. A. M.Hassan, M. A. E. Shaban, “Synthesis ofCarbohydrate-containing Polyamides andStudy of their Properties,”Eur. Polym. J.26(1990) 267 – 276.

178. L. Chen, D. E. Kiely, “Synthesis ofStereoregular Head/Tail Hydroxylated NylonsDerived from D-Glucose,”J. Org. Chem.61(1996) 5847 – 5851; US 5 329 044, 1994;Chem. Abstr.122(1994) 56785.


179. A. Gandini, M. N. Belgacem, “FuranicPolyamides Chemistry,”Progr. Polym. Sci.22(1997) 1238 – 1246.

180. A. Mitiakoudis, A. Gandini,“Poly(p-phenylene)-2,5-furandicarbonamideand Conversion into Filaments and Films,”Macromolecules24 (1991) 830 – 835.

Химические картинки, клипарт::Chemfiles ... - 2....

Documents

Transcript of Химические картинки, клипарт::Chemfiles ... - 2....