Michael Sinnott received his first degree in Chemistry from University of Oxford in 1966 and a PhD in Organic Chemistry from Bristol in 1968. After a postdoctoral at Stanford in Bioorganic Chemistry, he returned to Bristol and progressed up the academic ranks until he left, as Reader in Bioorganic Chemistry, in 1987 to become Professor of Chemistry at the University of Illinois at Chicago. He returned to the United Kingdom in 1996 for family reasons becoming Professor of Paper Science at UMIST. Progression of longstanding orthopaedic problems facilitated his retirement from UMIST, but he continues his scholarly and research supervision activities at University of Huddersfield. He has published 120 research papers, two books, and edited and contributed to the four-volume set ""Comprehensive Biological Catalysis"".

Carbohydrate Chemistry and Biochemistry

Structure and Mechanism

By Michael Sinnott

The Royal Society of Chemistry

Copyright © 2013 Michael Sinnott
All rights reserved.
ISBN: 978-1-84973-327-4

Contents

Chapter 1 Structures of Open-chain Forms of Reducing Sugars and Related Molecules Mechanistic Probes of Sugar Carbonyl Group Additions,
Chapter 2 Conformations of Sugar Rings and Glycosidic Linkages,
Chapter 3 Nucleophilic Substitution at the Anomeric Centre,
Chapter 4 Enzymic Glycoside Hydrolysis and Transglycosylation: Kinetics and Mechanism,
Chapter 5 Primary Structure and Conformation of Oligosaccharides and Polysaccharides,
Chapter 6 Heterolytic Reactions of OH Groups,
Chapter 7 Heterolytic Chemistry of the Carbon Chain,
Chapter 8 Glycosyl Transferases and Oligosaccharide and Polysaccharide Biosynthesis,
Chapter 9 Glycoconjugates: Biosynthesis and Properties,
Chapter 10 One-electron Chemistry of Carbohydrates,
Appendix,
Subject Index,

CHAPTER 1

Structures of Open-chain Forms of Reducing Sugars and Related Molecules. Mechanistic Probes of Sugar Carbonyl Group Additions

1.1 DEFINITIONS AND STRUCTURES

1.1.1 Definitions

Historically, carbohydrates were defined as substances with the empirical formula C(HO) The common sugars such as glucose and fructose (n=m=6), or sucrose (n=12, m=11) fit this formula, but nowadays the convention is to regard as a carbohydrate a polyhydroxy aldehyde or polyhydroxy ketone with the classical formula, a molecule closely related to it, or oligomers or polymers of such molecules. Their study evolved as a separate sub-discipline within organic chemistry for practical reasons – they are water-soluble and difficult to crystallise – so that their manipulation demanded different sets of skills from classical "natural products" such as terpenes, steroids, alkaloids, etc.

The term "monosaccharide" refers to a carbohydrate derivative possessing a single carbon chain; "disaccharide" and "trisaccharide" refer to molecules containing two or three such monosaccharide units joined together by acetal or ketal linkages. "Oligosaccharide" and "polysaccharide" refer to larger such aggregates, with "a few" and "many" monosaccharide units, respectively. Current usage seems to draw the distinction between "few" and "many" at around 10 sugar units.

The everyday term "sugar" is used to describe mono-, di-, and the lower oligosaccharides, particularly when unprotected. The historical term "reducing sugar" is still useful to describe a carbohydrate with a free carbonyl group, or one masked only by internal hemiacetal or hemiketal formation. The term arose because nineteenth-century physiologists and chemists had to rely on colour reactions, many of which are now known to involve single-electron transfers to transition metal complexes (e.g. Fehling's solution, Cu–tartrate complexes). Colour changes are observed if an ene diol structure (R-CH(OH) CH(OH)-R) or similar can be formed under the conditions of the test, since its anion readily loses an electron to form a resonance-stabilised radical. Therefore, both polyhydroxy aldehydes (aldoses) and polyhydroxy ketones (ketoses) are reducing sugars. 2-Deoxy- and 2-acetamido sugars also give enolates subject to one-electron oxidation, and hence are reducing sugars, though the amino sugars were usually assayed by the Morgan–Elson test (see Chapter 10).

1.1.2 Straight-chain Structures of Reducing Sugars Cn(H2O)m

All common sugars have an unbranched carbon chain, and are referred to as trioses (3 carbons), tetroses (4), pentoses (5), hexoses (6), heptoses (7), octoses (8) and nonoses (9). Depending on whether the carbonyl group is an aldehyde or a ketone, the monosaccharides are referred to as aldoses or ketoses, although IUPAC nomenclature prefers "-uloses", as in "hexuloses", for ketoses.

It is amazing to realise that the stereochemistry of glucose and related aldohexoses was deduced by Emil Fischer in the 1891, less than 20 years after van't Hoff's and Le Bel's postulation that the valencies of carbon were directed towards the apices of a tetrahedron. Fischer had only two physical parameters with which to characterise compounds (optical rotation and melting point), but nonetheless succeeded by rigorous stereochemical logic.

There are three trioses – a ketose (dihydroxyacetone) and the two enantiomeric forms of glyceraldehyde. In the carbohydrate field the R, S system of designating stereochemistry of a chiral centre, used elsewhere in organic chemistry, becomes very cumbersome, and Fischer's original conventions, as modified by Rosanoff, are still used (Figure 1.1).

The first Fischer convention is that the four bonds to a chiral centre are written horizontally and vertically, with the vertical bonds going in to the plane of the paper and the horizontal bonds coming out. Such Fischer structures can be rotated through 180° in the plane of the paper, but not through 90°, since then the convention would be violated.

The second Fischer (strictly, Fischer–Rosanoff) convention is that if the main carbon chain is written vertically, with the carbon of highest oxidation state (in the case of glyceraldehyde, the CHO group) at the top, then if the bottom asymmetric centre has the –OH on the right-hand side, the configuration is D-; if it is on the left-hand side, it is L-. This rule for designating the absolute configuration as D- or L- also applies to sugars with more than one asymmetric centre.

The aldotetroses have two non-equivalent chiral centres, so there are four (2) stereoisomers, made up of two pairs of enantiomers. Enantiomers have identical chemical and physical properties, except where they interact with agents which are themselves chiral. However, because the distances between atoms in different diastereomers differ, they have different physical properties, and different chemical properties towards achiral reagents. Thus, erythrose and threose have different melting points and different reactivities to achiral reagents. This can be grasped intuitively by considering the oxidation of these sugars to the corresponding lactones: in threonolactone the hydroxyl groups are trans, in erythronolactone they are cis (Figure 1.2).

The carbonyl groups of aldoses and ketoses, like other aldehydes and ketones with electron-withdrawing substituents, are hydrated in aqueous solution. Participation of one of the hydroxyl groups to give an internal cyclic hemiacetal also occurs, and indeed largely predominates where relatively strain-free five- and six-membered rings result. Aqueous solutions of aldoses and ketoses thus consist of a slowly equilibrating mixture of various species, of which the unhydrated straight-chain structures shown in this section are a very minor proportion. Compositions of equilibrated solutions of reducing monosaccharides are given in Table 1.1.

If the two ends of the carbon chain of erythrose are made identical (for example, by reducing the aldehyde to a CHOH group with NaBH), then the resulting alditol (erythritol) is achiral, since it contains a mirror plane. Erythritol is termed a meso form, and is internally compensated (i.e. one asymmetric centre is R and the other is S) (Figure 1.3).

Extension of the carbon chain of an aldose from the carbonyl by one unit at a time can be carried out fairly readily by the Kiliani reaction. A...