Glycoteam GmbH
Acros Organics Acta 10 - Spring 2003

GLYCALS
Extensive, interesting and inexpensive starting materials
for building blocks synthesis

Glycals, 1,2-unsaturated derivatives of pentaoses or hexaoses, which are readily made from 1-halogeno sugars by reductive elimination with zinc, were discovered by Emil Fischer and Karl Zach 1 in 1913. Due to theirs enol ether structure they demonstrate high and versatile reactivities and are among the most and variously transformable monosaccharide derivatives 2.

Because of that glycals can be ideally employment in the synthesis of carbohydrate derivatives as well as many other natural products. Especially in different addition, rearrangement and substitution reac- tions they show amazingly versatile properties. Not surprisingly, gly- cals are also subjects of considerable interest in combinatoral chem- istry and, as chiral building blocks, have been precursors for a broad variety of optical active products and for oligosaccharide synthesis 3. The very important transformations involve Lewis acid induced rearrangements, cycloadditions, oxidations or epoxidations.

The Lewis acid-catalyzed rearrangement of glycals in the present of different aglycons, known as the Ferrier rearrangement 4, is an

excellent method for the preparation of 2,3-unsaturated glycosides, which can be oxidized at the allylic position to enone 5. And sugar enones, because of presence of carbonyl group are used by whole series of addition reactions such as conjugate addition, cycloaddition and rad- ical addition.

A similar reaction to Ferrier reaction, which substitutes the alcohol with m-chlorperbenzoic acid leads to 2,3-unsaturated lactones 4. And the treatment of glycals with mercury sulfate/sulphuric acid leads to acyclic ,ß-unsaturated aldehydes. This reaction can be performed in good yield on many glycals 6.

Glycuronals under Ferrier conditions and with hydroxy acids as agly- cons did not react to 2,3-unsaturated glycosides but rather to novel class of 1,3-disubstituted derivatives 7.

The utility of glycals as precursors was also shown the synthesis of ionophors, leukotriens or C-glycosides 8, which in turn were frequent- ly used as chiral starting materials for the access to natural products.

Glycals are also very significant starting materials for stereoselective preparation of important of 2-amino sugars, building blocks needed in glycoconjugate synthesis, as well as oxetanes or ß-lactams 9.

Further glycals could be also used in chemoenzymatic synthesis of oligosaccharides and rare sugars. Recently glycal derivatives were studied as glycosidase and glycosyl transferase inhibitors and have
been used as antigens to raise antibodies 10.

A very rare Sialyl-Lewis X glycal, which was developed in Danishefsky’s group, is a moderate inhibitor of a-1,3-fucosyltransferase and has been successfully utilized for completing the total synthesis of sialyl-Lewis X antigen 11.

The substitution reactions of the O-benzylated glycals with t-butyllithium gives the lithiated intermediates, which with tributyltin chloride are converted into the stannylated glycals. Compounds of this tape can be further converted into C-aslyglycals, idoanalogues or sulphones.

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1. E. Fischer, K. Zach, Chem. Zentralblatt, 1913 I, 1968.
2. R. J. Ferrier, Adv. Carbohydr. Chem. Biochem. 20 (1965) 67-137. 24 (1969) 199.
3. S. J. Danishefsky, M. Biodenau, Angew. Chem., Int. Ed. Engl. 1996, 35, 1380.
4. R. J. Ferrier, N. J. Prasad, J. Chem. Soc. C 1969, 570.
5. B. Frasser-Reid, A. McLean, E.W. Usherwood, M. Yunker, Can. J. Chem. 48 (1970), 570.
6. J.Wengel, J. Lau, E. B. Pedersen, Synthesis 1989, 829.
7. E. Wieczorek, J. Thiem, Synlett, 1997, 467.
8. H. H. Postema, C-Glycosides Synthesis, CRC Press, London, 1995.
9. R. U. Lemieux, R. M. Ratcliffe, Can. J. Chem. 57 (1079) 1244.
10. J. Yu, J. Bioorg. Med. Chem. 6 (1998) 1145.
11. S. J. Danishefsky, J. Gervay, J. M. Peterson, F. E. McDonald, K. Koseki, T. Oriyama, D. A. Griffith, J. Am. Chem Soc. 114, (1992) 8329.
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