Cover Picture: Chem. Eur. J. 1/2003

Abstract

AbstractThe cover picture shows schematically a general, modular strategy for the first completely stereoselective synthesis of defined heparin oligosaccharides. Heparin is currently used as an anticoagulant to prevent the formation of thrombi. A developing thrombus is depicted as background. Di‐ and trisaccharide modules were derived from six monosaccharide building blocks in a fully selective fashion by placing a conformational constraint on uronic acid glycosyl acceptors. A new concept for stereochemical control of α‐glucosamine glycoside formation was utilized. Locking the conformation of the glucuronic acid acceptor allowed for completely selective preparation of the desired cis‐glycosides. This innovation greatly simplified the key step in the preparation of disaccharide building blocks. Combination of disaccharide modules to form trans‐uronic acid linkages proved also completely selective by virtue of C2 participating groups. Coupling reactions between disaccharide modules exhibited sequence dependence. Elaboration of disaccharide building blocks to trisaccharide modules allowed for stereoselective access to oligosaccharides as demonstrated on the example of a hexasaccharide. Final deprotection and sulfation yielded the fully synthetic heparin oligosaccharides. A detailed description of this study is reported by P. H. Seeberger et al. on p. 140 ff.