Introduction and General Aspects

Review material published this year includes an essay 'the unexpected and the unpredictable in organic synthesis' which is a valuable account by Mukaiyama of the extraordinary history of his research, sections on stereoselective routes to sugars and glycosides being of special relevance.

As the subject continues to be driven increasingly by biological challenges a larger proportion of the text/review literature reflects this trend. The third of a series of major texts on Bioorganic Chemistry entitled 'Carbohydrates' follows two on nucleic acids (1996) and proteins (1997). Thirteen chapters by distinguished authors are introducted by Professor Ray Lemieux whose death in 2000 marked the end of the most notable of modern carbohydrate chemical careers. The topics covered in the book lay appropriately heavy emphasis on glycobiological aspects of the subject.

Two volumes of Advances in Carbohydrate Chemistry and Biochemistry appeared in 1999, one taking the form of useful Tables of Contents, and Subject and Author indices for volumes 1–53, the first of which appeared in 1945. The other contains obituary notices on Lord Todd, Professor Melvin Calvin and Dr Margaret A. Clarke, the first two winning Nobel Prizes for their work which illuminated issues associated with the roles played by the carbohydrates in natural processes, and the third making major contributions to sugar chemistry within the industrial/commercial scene. The volume also contains reviews on A-thiocarbonyl derivatives of sugars – isothiocyanates, thioamides, thioureas and thiocarbamates (J.M. García Fernández and C. Ortiz Mellet), the synthesis of chiral polyamides from carbohydrate-derived monomers (O. Varela and H.A. Orgueira) and hydrazine derivatives of carbohydrates (H. El Khadem and A.J. Fatiadi).

An extensive range of other reviews has been published, many being referred to at the beginning of relevant chapters. Of general significance are assessments of recent developments in polymer-supported syntheses of oligosaccharides, of recent advances in solid- and solution-phase methods relevant to the generation of carbohydrate and glycoconjugate libraries and of the use of carbohydrates as molecular scaffolds for library synthesis, of the preparation of biologically active carbocyclic oligosaccharides and their structure-activity relationships as glycosidase inhibitors, and of the synthesis of 'glycopolymers' made from sugars with natural and unnatural linkages and from copolymers comprising carbohydrates in part.

Further reviews of relevance in glycobiology have dealt with the synthesis and function of glycoconjugates, with recent developments in this field and with the use of carbohydrate mimetics in the study of carbohydrate-mediated biomolecular recognition. Bertozzi has reported on her new approaches to the preparation of stable C-glycosidic glycopeptide mimetics.

Of general relevance in glycobiology is a review of the impact of evolutionary considerations in respect of oligosaccharide diversity and biological function. A paper on single yeast cell studies of the enzymic hydrolysis of a tetramethylrhodamine-labelled triglucoside could revolutionize in vitro whole cell analysis of oligosaccharide processing, and the finding that low molecular weight dextrans enter the nucleus and are better inhibitors of breast cancer cell growth than are larger oligomers is of obvious potential value.

Free Sugars

1 Theoretical Aspects

AMI and ab initio calculations performed on D-glucopyranose and its monoalkoxy anions indicated that the C-1- and C-4-hydroxyl groups are the most acidic for the α- and β-anomers, respectively. In all cases, the primary hydroxyl group was the least acidic.

In a molecular dynamics study on the hydration properties of an 85 w/w aq. solution of glucose, the radial distribution function, H-bond residence times, hydration number, and the mean life time and size of glucose and water clusters have been computed, and in a theoretical investigation of the mutarotation of glucose assisted by up to five H2O molecules the participation of water dimers and trimers, which provide a strain-free hydrogen bond network for ready H-transfer, has been considered.

2 Synthesis

A paper entitled 'The unexpected and unpredictable in organic synthesis' covering Mukaiyama's work in the aldol condensation field contained a section on the synthesis of carbohydrates from D-glyceraldehyde and L-erythrose.

2.1 Tetroses and Pentoses. – All D-tetroses and D-pentoses have been synthesized from 2,3-O-isopropylidene-D-glyceraldehyde by consecutive one-carbon chain-elongation using the Li salt of ethyl ethylthiomethyl sulfoxide. The additions proceeded with high anti-diastereoselectivity and the formations of the major products, D-erythrose and D-ribose, are outlined in Scheme l.

D-Xylose has been converted into D-lyxose via mesylate 1, which on treatment with one molar equivalent of NaOH in aqueous DMF gave 2, possibly by way of the l,2-β-D-lyvo-epoxide. Conversion of D-xylose into L-xylose involved resolution of the racemic xylitol derivative 3 by lipase-catalysed hydrolysis to give a mixture of the D-alcohol and unreacted L-acetate. The latter was hydrolysed chemically, then oxidized (Pfitzer Moffat) and deacetalized. L-Xylose was the starting compound for the synthesis of L-ribo-nucleosides, the required inversion of configuration at the 3-position being achieved by oxidation-reduction (CrO3/pyridine-LAH). In the synthesis of [3,4,5',5"-2H]-ribonucleosides from diacetone-D-glucose, the deuterium atoms were introduced consecutively by reduction of a keto group with NaBD, hydrogen-deuterium exchange α to an aldehyde using D2O and reduction of an ester group with LiAlD4, as shown in Scheme 2.

The synthesis of racemic, fluorinated xylulose derivatives based on a Wittig approach and two syntheses of labelled 1-deoxy-D-xylulose are covered in Chapters 8 and 15, respectively, and the preparation of 3-deoxy-3-C-methylene-pentofuranosides (as...