Benzyloxycarbonyl protected thioglycosides for diastereoselective glycosylation

Abstract

In nature, various glycoconjugates are widely used by organisms for instance in cell communication processes, as scaffold molecules, or to increase the water-solubility of apolar compounds. Enzymes produce ß-anomers, mainly. Plenty of these substances only occur in very small amounts which often leads to difficulties in isolation. Therefor, the usage of synthetic methods is of great interest to make them easier accessible. Additionally, molecular modifications are usually straightforward. In chemical glycosylation, formation of a glycosidic bond takes place between a glycosylic donor and an acceptor molecule. Depending on this acceptor, oligosaccharides or glycosides are synthesized. During the reaction, a new stereogenic centre emerges , causing a mixture of alpha- and beta- product. Acceptor molecules are often very expensive. Furthermore, separation of anomeric mixtures without much loss is a tough task. As a result of this, glycosylic donors for diastereoselective glycosylation are desirable. Up to this point, the selectivity problem was solved, using ester functionalities as protective groups, which favours the formation of ß-anomer due to a participating neighboring group effect. Unfortunately, this method can't be applied for acceptors, that contain ester groups. Cleavage of the protective groups may harm the product's ester functionalities as well. This thesis aims at the implementation of Benzoxycarbonyl- (CBz) and 2-(2-Benzyloxyphenyl)acetyl- (BnPAc) as novel participating protective groups, that can be cleaved orthogonally. Furthermore, the removal of by-products, that are formed during the deprotection step is simple. Thioglycosides are particularly suitable for the planned application, because they can be activated under mild conditions using lewis acids and show excellent storage capabilities. For the donor synthesis, two different approaches should be used. Besides the thioorthoester-strategy, already known to literature for similar substances, the dihydroxylation of glucals should be developed as a novel method. The key advantage is a reduction of the necessary reaction steps. Various donor types, including fluoroglycosides and glycosylimidates, should be made accessibly by anomeric modifications. Moreover, several acceptor molecules should be glycosylated using different donors and activation strategies. The diastereoselectivity has to be confirmed by NMR-spectroscopy.