Recent developments in the synthesis of g I ycocon j ug ates

The biological significance of glycoconjugates has stimulated a great synthetic activity in the synthesis of these structurally demanding compounds. These efforts were in the beginning mainly concentrated on improvements of the well-known KOENIGS-KNORR METHOD providing finally a very valuable methodology for glycoconjugate synthesis. However, due to several, mainly inherent disadvantages other anomeric oxygen exchange reactions have been investigated for the generation of glycosyl donor properties. For instance, GLYCOSYL FLUORIDES and SULFIDES and their activation with fluorophilic and thiophilic catalysts, respectively, was studied in several laboratories, as shortly discussed. Other activation principles were investigated in our laboratory, namely the base catalyzed activation retaining the anomeric oxygen atom. This led to the direct ANOMERIC 0ALKYLATION procedure with primary triflates as the alkylating agents providing a most convenient method for glycoside bond formation due to its simplicity and the yields and stereoselectivities obtained. However, the direct base catalyzed activation with trichloroacetonitrile afforded O-glycosyltrichloroacetimidates which are in terms of stability, reactivity, and general applicability outstanding glycosyl donors. The scope of this TRICHLOROACETIMIDATE METHOD is summarized in this paper. INTRODUCTION The presence of complex carbohydrate structures as integral constituents of membranes and cell walls has led to manifold activities in recent research (ref. 1 ) . An especially important role amongst these glycoconjugates seem to play the glycosphingolipids, the glycophospholipids, and the glycoproteins. Their manifold functions more and more recongnized only very recently (ref. I-4), are based on a great structural diversity of the oligosaccharide portion, which is inherent to the variability in glycoside bond formation (ref. 1,3). This point was recently impressively illustrated (ref. I ) , rendering oligosaccharides ideal as carriers of biological information and specificity. The biological significance of glycoconjugates should be viewed by the synthetic chemist as a major challenge (ref. 1): The synthesis and modification of the oligosaccharidic moieties and their coupling with appropriate lipids, phospholipids, and proteins is essential to extend our knowledge on the molecular mode of action of glycoconjugates and to derive new principles of physiological activity. Due to the great structural variability on the different structural levels, homogeneous compounds are often only with great difficulty accessible from biological material. GLYCOSYL DONORS VIA ANOMERIC OXYGEN EXCHANGE REACTIONS: THE KOENIGS-KNORR METHOD A N D RELATED METHODS Indeed, the biological significance of glycoconjugates has stimulated a great synthetic activity in the last years (ref. 1 , 4 6 ) . However, these efforts were in the beginning mainly concentrated on improvements of the well known Koenigs-Knorr method for oligosaccharide and glycoconjugate synthesis (Scheme 1 , Path B) which finally led to a very valuable methodology. This methodology has been recently reviewed quite extensively (ref. 4,6). However, several