The applicant will seek to develop a new strategy for the synthesis of oligosaccharides. Adjacent carbohydrate units will be linked together via ester or thion ester bonds. Subsequent reduction, without C-O bond cleavage, will be used to unravel the glycosidic framework. Two distinct procedures will be investigated. Aldonic acids will be esterified with carbohydrate alcohols. Subsequent methylenylation and iodoetherification will be used to prepare oligosaccharides containing the aldose-ketose link. Additionally aldonic acid amides will be condensed with carbohydrate alcohols to produce aldonic thion esters. Reductive methylation and silver mediated cyclization of these species will be used to prepare di- and higher oligosaccharides. These redox glycosidation methods will be used to prepare reducing and non reducing disaccharides including maltose, trehalose, sucrose and lactose. The methods will additionally be employed in the construction of several sialic acid derivatives, poly beta-(1-4) glucopyranose and related species and cavity molecules that are analogs of beta-cyclodextrin and the cardiotonic agent digitoxin. Since oligosaccharides and glycoproteins serve a diversity of vital roles in biological systems, rational approaches to their synthesis are of fundamental importance. The classical procedure for their construction, the Koenigs-Knorr reaction in its many variations, has many disadvantages. Firstly Koenig-Knorr chemistry can not be easily iterated, for example, on a polymer support. Secondly the method is of little use in the elaboration of many biologically active materials, for example, the sialic acids. There is a need for a simple and general procedure to readily assemble oligosaccharides from aldose and ketose monomers. Success in this venture would be of very considerable importance in further understanding the roles of oligosaccharides in vivo.
| Barrett, A G; Melcher, L M; Bezuidenhoudt, B C (1992) Redox glycosidation: the use of Nozaki-Takai methylenylation in a highly stereoselective synthesis of sucrose. Carbohydr Res 232:259-72 |
