ORGN 223 |
| Glycopeptide antibiotics such as vancomycin, orienticin, ristocetin, and teicoplanin are known to exhibit strong biological activity and are useful in treatment of infectious diseases. Construction of the biaryl ether architectures in these glycopeptide antibiotics in high yield, under mild, non-racemizing conditions, remains a challenge for the synthetic organic chemist. Ruthenium-mediated nucleophilic aromatic substitution chemistry has previously been demonstrated in the assembly of biaryl ether linkages in the advanced intermediates of several glycopeptide antibiotics. The vancomycin and teicoplanin analogues in this class of natural products present atropisomerism induced by the presence of chlorine substituents on the C and E rings of their C-O-D and D-O-E biaryl ether linkages. This atropisomerism imparts stereochemistry that further complicates the formation of these biaryl ether bonds. In this study we aim to demonstrate ruthenium-mediated methodology applicable to the chemoselective closure of biaryl ether linkages in Vancomycin. We will illustrate the feasibility of these facile, chemoselective, nucleophilic aromatic substitutions to provide desired 16-membered Vancomycin-type macrocycles through selective displacement of mixed halogenated aryl ruthenium complexes.
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Metal-Mediated Reactions and Synthesis
8:00 AM-12:00 PM, Monday, April 7, 2008 Morial Convention Center -- Rm. R06, Oral
Division of Organic Chemistry |
