Introduction and General Aspects

The very unusual absence of a new volume of Advances in Carbohydrate Chemistry and Biochemistry limits the number of quality reviews to have been published this year, and those that have appeared tend to be referred to at the beginnings of relevant chapters. This chapter is therefore unusually brief.

Danishefsky and Roberge have summarized the Sloan-Kettering work on the use of glycals as glycosyl donors and acceptors in the synthesis of oligosaccharides of glycoconjugates. The use of enzymically derived cis-dihydroxylated aromatics as starting materials for the iterative preparation of oligo- nor-saccharides, -inositols and pseudo-sugars has been surveyed.

In the field of origin of life studies Eschenmoser and Kisakürek have discussed the potential biogenic relationship between hexose- and pentose-based nucleic acids, and a paper has appeared from the same group on the base pairing between oligonucleotides comprising pentopyranosyl D- and L-nucleotides.

Free Sugars

1 Theoretical Aspects

Molecular dynamics simulation calculations aimed at providing better understanding of the relative sweetness of β-D-glucopyranose, β-D-galactopyranose, and α- and β-D-mannopyranose failed to verify the hydrophobic G site hypothesis proposed by Tinti and Nofre (ACS Symp. Ser., 1991, 450, Chapter 15).

2 Synthesis

A comprehensive review (260 refs.) on the synthesis of carbohydrates from non-carbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni's thiazole and Vogel's 'naked sugar' approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three 'Aldol Reaction Kits' that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.).

A newly discovered NAD-dependent hydrogenase from celery oxidizes D-mannitol to D-mannose; several other pentitols and hexitols, especially those with the same absolute configuration at C-2 as that of D-mannitol, are oxidized to the corresponding aldoses at a slower rate.

2.1 Tetroses and Pentoses – 4-O-t -Butyldimethylsilyl-2,3-O-isopropylidene-D-threose (1) has been prepared in seven efficient steps from D-xylose. 3,4-O-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-O-isopropylidenehexofuranoses (e.g.,6 [right arrow] 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-glycero-pentos-2-ulose (8) to 3-deoxy-D-glycero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH. 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1.

The synthesis of [5-13C]D-ribose from D-ribose involved diol cleavage of the original C-4-C-5 bond and formation of a new C-4-C-5 bond using a 13C-enriched Wittig reagent. 3,4,5,5-d14 -DL-Ribose (12) has been obtained from dg-glycerol (11), as outlined in Scheme 2.

2.2 Hexoses – The synthesis of hexoseptanose derivatives by ring expansion of uloses, Baeyer Villiger oxidation of inositols, or Baeyer-Fischer reaction of sugar dialdehydes has been reviewed.

The methyl β-L-idoseptanoside derivative 14 was produced by oxidation/reduction (Ru2O-NaIO4/NaBH4) of the corresponding methyl β-D-glucoseptanoside 13. On transmetalation with InCl3, δ-oxygenated allylic stannanes undergo in situ addition to aldehydes furnishing predominantly anti products. This method has been applied to the synthesis of D-altrose as shown in Scheme 3. A similar route to α-L-daunosamine hydrochloride is covered in Chapter 9. The chemoenzymic synthesis of 6-substituted D-fructose analogues by use of epoxide 15 is referred to in Chapters 7, 8, 9 and 10, and that of 6-deoxy-L-sorbose in Chapter 12.

The best conditions for producing glucose with close to 100% H-isotope labelling at C-1, with negligible formation of labelled by-products, by exchange with deuterium or tritium gas in aqueous solution have been determined. Various 2H-labelled D-mannoses, as well as 2,3,4,5,6-d5- and 1,1,2,3,4,5,6,6-d8-D -mannitol, were obtained by ozonolysis/sodium borohydride reduction of the functionalized cyclohexene 16, which was obtained in enantiomerically pure form from 2H5-chlorobenzene following biological hydroxylation.

D-Tagatose 3-epimerase immobilized on Chitopearl beads effected the isomerization of L-sorbose and L-psicose to L-tagatose and L-fructose in 20 and 65% yield, respectively. Sequential use of pyranose 2-oxidase and hydrogen over palladium permitted the one-pot chemoenzymatic conversion of D-galactose to D-tagatose in 30% yield, whereas sodium borohydride reduction followed by microbial oxidation furnished D-sorbose from D-gulonolactone with high efficiency. A...