Acceptor glycoside synthesis

C-Glycoside synthesis via the intermolecular addition of anomeric radicals to activated alkenes has been pioneered by Giese and co-workers [120]. A wide variety of acceptors have been used in this area and both simple [131,132] and more complex (a C-disaccharide 290) [133] examples are shown (Scheme 77). 

The lactonized phenyl 2-thioglycosides of dimeric (26) [41] and trimeric (27) [42] sialic acids, which were prepared from the corresponding oligosialic acids according to the procedure employed for the monosialyl derivatives, were each coupled with the suitably protected sugar acceptors (14, 16, 17, and 19) by use of NIS-TfOH as a promoter in acetonitrile, as just described for the monosialyl glycoside synthesis (Fig. 3). 

In spite of the successful implementation of the concept of remote activation of an anomeric 2-pyridylthio group, there emerged various issues and questions. The absence of self-condensation products could be ascribed to the use of excess acceptor in all cases, and possibly to the coordination of the mercuric salt to the free hydroxy groups of the donor, thereby diminishing their reactivity. However, the necessity to use an excess of acceptor (> 5 eq), the formation of anomeric mixtures of glycosides, and the use of a mercuric salt, limited the generality of this method of glycoside synthesis. 

Despite its wide application in glycoside synthesis, the Koenigs-Knorr reaction suffers from several disadvantages (i) the glycosyl halides are unstable, (ii) excess toxic heavy metals are needed to activate the donor, and (iii) a desiccant (to absorb any liberated water) and an acid acceptor (to absorb the liberated hydrogen halide and can be a promoter itself) are often needed to increase the yield and suppress side reactions. 

K. G. I. Nilsson, A simple strategy for changing the regioselectivity of glycosidase-catalysed formation of disaccharides Part II, Enzymic synthesis in situ of various acceptor glycosides,... 

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