ORGN 589 |
Asymmetric total synthesis of carbocyclic sinefungin
| Marvin J. Miller1, Bohan Jin1, Namal C. Warshakoon2, and Jennifer L. Gage3. (1) Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, (2) Proctor and Gamble, (3) Eli Lilly and Company |
Nucleosides are regulators of important physiological functions in living organisms. The natural nucleoside (+)-sinefungin 1 exhibits strong antiviral, antifungal, and antiparasitic activities, however the clinical trials of sinefungin were greatly impeded due to its high toxicity. Based on SAR studies, we devised 2 as a sinefungin analog that hopefully will be less toxic while retaining the biological activities of the natural sinefungin. Our convergent approach features a key Pd(0) mediated coupling reaction to join allyl acetate 4 and b-ketoester 3 providing the full carbocyclic sinefungin backbone. The optically active acetate 5 was obtained through an enzymatic resolution of racemic alcohol 6, which was in turn derived from the acylnitroso [4 + 2] Diels-Alder adduct 7. Progress towards the total synthesis of 2 will be described. |
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Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses
11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster
Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003
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