Uncommon Sugars and Their Glycosylation

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This project is focused on the development of a ring closing metathesis (RCM) approach to produce a small library of uncommon sugars. By using a corresponding 1,2-glycal library as intermediates, the uncommon sugar library will be made more amenable for stereoselective glycosylation in the next step. Several new "thio-reagents" will be developed for the conversion of L- or D-rhamnal or L- or D-3-methylrhamnal to beta-1-thio-2-pseudoglycal through a SN2'-syn mechanism. From 8 alpha- & beta-1-thio-2- pseudoglycals, 32 glycals can be prepared by either functionalization of the C4 position through routine stereospecific transformations or/and by functionalization of C3 position through new sulfimidation chemistry. From the glycal library, 1-S-2-axial-I donors and novel 1-S-2-eq-(2- picolylthio) donors will be synthesized and evaluated for connecting the 2-heteroatom sugar 1-thioglycoside to an aglycon with specific alpha or beta configuration. This stereospecific glycosylation method will be used in an iterative one-pot approach to synthesize the 17 members of oligosaccharide in novel antibiotic Saccharimicins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Peng G. Wang, of the Department of Biochemistry at the Ohio State University. Professor Wang and his students are developing new chemistry and new reagents for the synthesis of uncommon sugars with great structural diversity. Uncommon sugars, which include deoxysugars, amino deoxysugars and branched-chain sugars, are frequently found in the secondary metabolites of microorganisms and plants, such as cardioglycosides, antibiotics, and anticancer agents. The sugar moieties of these pharmaceutically important metabolites play an important role in determining the biological activities of these natural products. Since uncommon sugars are extremely useful in the structure-activity-relationship (SAR) study of sugar containing bioactive natural products and pharmaceuticals, this research will provide a general chemistry platform and technology for medicinal chemistry and pharmaceutical industry.