Contemporary carbohydrate is being continually challenged by the ever expanding field of glycobiology and, more specifically, by the complexity and diversity of biologically and medically important oligosaccharides uncovered whose synthesis is mandated by their extremely tedious isolation and purification from natural sources in minute quantities. In spite of the remarkable recent advances in the synthesis of carbohydrates, many of which could not have been contemplated more than a few years ago, there still remains many important problems in carbohydrate chemistry to be addressed before the full potential of the field of glycobiology can even begin to be realized.
The aims of this project are to provide efficient, effective syntheses of beta-L- and beta-D-rhamnosides and further improved methods for the beta-D-mannosides in both the solution and solid phases. These targets are being pursued with a view to the synthesis of the antigenic capsular polysaccharides from the various strains of Streptococcus pneumoniae, all of which have the beta-L-rhamnoside linkage the core of the repeating unit. These capsular polysaccharides are components of multi- valent vaccines used for the prevention of pneumococcal infections, which remain a significant cause of morbidity worldwide especially given the increasing numbers of antibiotic resistant pneumococci. A further aim is to synthesize the common exopolysaccharide repeating units from Escherichia hermannii ATCC 33650 and 33650, which has a beta-D-rhamnopyranoside at its core. This is a very different problem, requiring a different solution to that of the Streptococcus pneumoniae capsular polysaccharides, as D-rhamnose, unlike L-rhamnose, is not readily available and so cannot be used as starting material. It is intended to develop all of the methods in both the solution and polymer-supported systems. Both have their role to play in the future of carbohydrate chemistry, with the solution methods probably remaining optimal for large quantities of smaller oligosaccharides, and the polymer supported methods being required for the production of pure, longer oligomers. Accordingly, it is necessary that any truly valuable method be demonstrated to be readily transferable between the two phases.
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