Stereoselective glycosylations using control

Therefore, to obtain complete stereoselectivity, the entire glycosylation process has to be performed in a highly controlled manner. In this particular case, the control is achieved by the use of extremely mild catalyst (I NBr), although very reactive substrates and prolonged reaction at times are required. 

New strategies for preparing either 1,2-cis- or 1,2-trans-glycosides stereoselectively have been reported.61 A chiral auxiliary containing a nucleophile is used to control the anomeric selectivity of the glycosylation. A sample reaction is shown in Scheme 8. 

The presence of an equatorially substituted cyclic sulfonium intermediate 7 that controls the stereoselectivity of glycosylation was confirmed by nuclear magnetic resonance (NMR) spectroscopy. Combined use of this methodology to introduce a-glycosides and traditional /3-glycoside protocols provides a potential route to one-pot multistep glycosylations and automated syntheses for a wide variety of oligosaccharides. 

SCHEME 3.27 Stereoselective control of glycosylation by using glycosyl epoxide. TBAF, tetrabutylammonium fluoride. 

A different approach to control the stereoselectivity of glycosylations is through the use of heterogeneous catalysis. Catalysts such as silver silicate were developed for this purpose [46]. Reactions of glycosyl halides on the surface of silver silicate are thought to proceed by a concerted mechanism providing, for example, (3-D-mannopyranosides 44 from a-D-mannosyl bromide 43 (Scheme 4.7). 

In an effort to address the medicinal chemist s need for new synthetic methods for the preparation of unnatural carbohydrates, new de novo methods for carbohydrate synthesis have been developed. These routes use asymmetric catalysis to set the sugar absolute stereochemistry, a palladium-catalyzed glycosylation reaction to stereoselectively control the anomeric center, and subsequent diastereoselective post-glycosylation to install the remaining sugar stereocenters. The utility of this method has been demonstrated by the syntheses of several classes of mono-, di- and tri-saccharides. 

---