Protecting glycosidases

Recent developments in the enzymatic synthesis of carbohydrates can be classified into four approaches 1) asymmetric C-C bond formation catalyzed by aldolases (1-10 2) enzymatic synthesis of carbohydrate synthons (loll) 3) asymmetric glycosidic formation catalyzed by glycosidases (12.-17) and glycosyl transferases (18-23.) and 4) regioselective transformations of sugars and derivatives (24-25). These enzymatic transformations are stereoselective and carried out under mild conditions with minimum protection of functional groups. They hold promise in preparative carbohydrate synthesis. In connection with this book, we focus on the first two approaches. 

Recently McDonald et al. reported the synthesis of (1 —> 5)-linked D-mannoseptanosyl di- and trisaccharides.80 Once again they utilized differentially protected phenyl 1-thio-a-D-mannoseptanoside as donor and methyl a-D-mannoseptanoside as acceptor to synthesize the di- and tri-a-septanosides exclusively. The strategy used for their synthesis mirrored that depicted in Scheme 26. The septanoside structures and their properties in a glycosidase assay are presented in Section IV. 

Addition of pyruvate to Cbz-protected D-mannosamine 194 under NeuA catalysis has furnished an JV-acyl derivative of neuraminic acid 5 from which internal reductive amination yielded an azasugar which could be further elaborated to 195, an analog of the bicyclic, indolizidine type glycosidase inhibitor castanospermine [91]. 

Using this type of chemistry, more than 30 different iminoalditols have been synthesised without using any protecting group strategy, and a number of new glycosidase inhibitors have been identified (2,12,13,14). Some selected interesting features will be discussed below. 

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