Introduction and General Aspects

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

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

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

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

Free Sugars

1 Theoretical Aspects

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

2 Synthesis

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

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

In the transketolase-catalysed condensation (see Vol. 27, Chapter 2, Refs. 6, 16) of...