This project is concerned with development of practical synthetic chemical methodology in the field of carbohydrates of biological significance, and the application of useful techniques to the synthesis of carbohydrate biomolecules, their components, and therapeutically promising analogs. Areas of synthesis will emphasize convenient transformations under mild conditions leading to important modified sugars, including deoxy sugars, aminopolydeoxy sugars, and their glycosidic conjugates. Reactions for study focus on novel blocking-group strategy in procedures for sequential oligosaccharide synthesis, routes to higher-carbon sugars and C-glycosyl heterocycles, and the use of unsaturated sugars as chirality-transfer precursors for synthesis of asymmetrically substituted carbocycles. Structural classes towards which these syntheses are directed include carbohydrate antibiotics, especially of the aminocyclitol, anthracycline, and nucleoside groups, the carbohydrate portions of glycoproteins, blood-group determinants, and other carbohydrates that are carriers of biological information, and noncarbohydrate chiral molecules such as prostaglandins and various cholinomimetic agents. In addition to the development of general procedures, specific targets for synthesis include new antitumor-active adriamycin analogs, C-nucleosides, acyclic-sugar nucleoside analogs of novel constitution, and analogs of aminocyclitol antibiotics based on a carbon-linked pseudodisaccharide structure. Detailed biological studies will be performed as appropriate on target molecules, with particular emphasis on antitumor properties.
