This project is directed towards the development of new methodology for the chemical synthesis of biologically important carbohydrates, and the application of useful techniques for the convenient preparation of carbohydrate and related biomolecules and structural variants which are of potential biochemical and medicinal utility. Aspects of reactivity and chemical mechanism are explored concurrent with the synthetic endeavors. Fundamental studies in general synthetic methodology will focus on the application of organometallic reactions for functionalization and homologation of mono- and oligosaccharides, on deoxygenation and skeletal rearrangements for the preparation of deoxy and branched-chain sugars, on halogenation (especially fluorination) and amination of carbohydrates, on synthesis and the study of reactivity of amino-nitro sugars, and on progressive glycosylation of higher hetero-oligosaccharides. Biologically significant, structural categories in which these researches will be performed include aminodeoxy and aminopolydeoxy sugars, aminocyclitols, and deoxy sugars important in the arenas of antibiotics chemistry and bacterial antigen structure, carbohydrate components of glycoproteins and glycolipids, and cyclodextrin analogs. Specific targets which will be approached in addition to these methodological investigations are aminated, configurational analogs of the natural disaccharide Alpha,Alpha-trehalose that show promise as antituberculous agents; chiral derivatives of 2-deoxy-streptamine for use in aminoglycoside antibiotics synthesis and mutasynthesis; and new, carbohydrate-modified analogs of antitumor-active anthracyclines, which may show enhanced activity or diminished toxicity.
