The problem of the stereoselectivity of glycosylations is a crucial issue of carbohydrate chemistry since its early days. A multitude of factors are known to affect this seemingly simple reaction, nevertheless, the outcome of an actual glycosylation is still hard to predict and a highly desired, universally applicable, stereoselective glycosylation method is still not in sight.
The conformational preferences of the gylcosyl donors and - more importantly - those of the activated intermediates (the actual glycosylating species) received much attention recently. The conformational shift caused by bulky protecting groups have been used to prepare „axial rich” glycosyl donors and to study conformational effects on glycosylations. Interpretation of the results, however, is complicated by the delicate conformational balance of these derivatives in the ground state, which makes conformations in the activated state even less predictable. Conformational locking by covalent bonds induces more constraints both in the ground and in the activated states and, therefore, makes the observed stereoselectivities more conclusive in terms of conformational effects.
In a systematic study of factors affecting the stereoselectivities of glycosylations we have investigated the conformational effects of glycosyl donors on the stereoselectivity. Conformational-locking resulting in inverted conformations has been accomplished by bridging different positions (i.e. O-2 and O-4, or O-3 and O-6) of pyranoses of different configurations. Glycosylations with these bridged glycosyl donors against a standard set of glycosyl acceptors have been studied. It was found, that several of the conformationally-locked glycosyl donors react with complete or very high stereoselectivity.
