Manipulation of Sugar Hydroxyl Groups

Epoxides have already been discussed in the context of suitable electrophiles for the introduction of halides and amines to sugar scaffolds. Complementary to these discussions, epoxides are also useful 

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The chemical transformations of dialkyl dithioacetals have been reviewed in detail [47] and offer routes to a variety of useful carbohydrate derivatives. Dialkyl dithioacetal derivatives of sugars continue to play an important role in modem synthetic carbohydrate chemistry through reactions of die dithioacetal function and manipulation of the sugar hydroxyl groups. Dithioacetals also provide a convenient method for temporary protection of sugar carbonyl groups in the synthesis of noncarbohydrate natural products. 

Prom the viewpoint of a synthesis chemist, carbohydrates would appear to be severely overfunctionalized. Thus, in a hexopyranose, one has to contend with five hydroxyl groups distributed over six carbon atoms. Furthermore, four of the hydroxyl groups are chiral. Obviously, to cany out synthetic manipulations on such molecules one has to learn to protect hydroxyl groups (or amino groups in the case of aminodeoxy sugars) to leave free only those destined for reactions. Therefore, a rich repertoire of protecting gronp manipulations for this purpose has evolved [1,2]. Table 1 shows some of the more common ones in current use. 

Other macrohdes have been prepared which represent hybrids of stmctures within the 14-membered family, within the 16-membered family, or between the two families. These hybrids have been made by chemical, bioconversion, or genetic manipulations. The 9-0-[(2-methoxyethoxy)methyl]oxime of tylosin (Table 7) was synthesized, using the oxime found in roxithromycin (33) (369). 3-0-Cladinosyl derivatives of 16-membered macrohdes were synthesized in which the neutral sugar of erythromycin (Table 3) was attached to tylosin derivatives at thek 3-hydroxyl group, analogous to its position in erythromycin... 

The manipulation of appropriately activated hydroxyl groups by nucleophilic displacement reactions is an indispensable tool for the introduction of functionalities directly attached to the sugar framework. 

The introduction of an olefin at the anomeric position is synthetically interesting as it permits, via ozonolytic cleavage, access to the anomeric aldehyde, useful for further manipulations. Furthermore, the cleavage of the tether after cyclization releases one hydroxyl group selectively, which may be used chemoselectively in subsequent reactions. This reaction was also shown to be applicable to furanose sugar derivatives [2]. 

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