NEW ASPECTS OF GLYCOSIDE BOND FORMATION
Richard R. Schmidt
Fakultät Chemie, Universität Konstanz, Fach M 725,
D-78457 Konstanz, Germany
The chemical synthesis of oligosaccharides has seen years of dynamic progress,
mainly based on highly reactive glycosyl donors, versatile building block
strategies, and advanced protective-group design during the last two decades
(1). The endeavour was stimulated by the eminent role of carbohydrates
and especially of glycoconjugates in various fields of modern biology (2).
A prominent area in this regard is glycoconjugate synthesis which is essentially
based on suitable monosaccharide building blocks, their regio- and diastereoselective
glycosidic linkage, and finally removal of the protective groups. A central
role plays glycoside bond formation because of its difficulty in arriving
at high chemical yields and diastereocontrol. Major progress has been made
for aldoses in recent years. However, improvement in sialylation, e.g.
ketoside formation, arriving at gangliosides, is an important task, because
further knowledge of the biological function of gangliosides should result
from such endeavours. In chemical ganglioside synthesis, sialylation has
been carned out by various methodologies (3). Consideration of various
leaving groups led us to phosphite (and phosphate, the in vivo glycosyl
donors) moieties and their derivatives. Thus, a readily available O-acetylated
neuraminic acid derivative is transformed into a sialyl donor which with
alcohols as acceptors and in nitriles as solvent provides the target molecules.
Recent results and extensions of this approach will be discussed.
Despite of these synthetic achievements, the synthesis of large and complex
oligosaccharides in solution remains a demanding task. A well established
method for the preparation of oligosaccharides (homo- and heteroglycans)
at a solid phase could be superior to solution trechniques in respect to
efficiency, future automatization, and application in combinatorial synthesis.
Our efforts on the investigation of solid phase glycosylations (4) will
be reported.
1. R.R. Schmidt, Angew. Chem., 98, 213-236 (1986); Angew. Chem. Int. Ed.
Engl., 25, 212-235 (1986); R.R. Schmidt, in Glycosciences: Status and Perspectives
(Eds. H.J. Gabius, S. Gabius), Chapman and Hall, Weinheim,1997.
2. R.A. Dwek, Chem. Rev., 96, 683 (1996).
3. T.J. Martin, R.R. Schmidt, Tetrahedron Lett., 33, 6123-6126 (1992);
G. Hummel, R.R. Schmidt, Tetrahedron Lett., 38,1173-1176 (1997).
4. J. Rademann, R.R. Schmidt, Tetrahedron Lett., 37, 3889-3990 (1996);
J. Org. Chem. in print.