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Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase
Ella Fitterer1, Jean-Luc Montchamp1
1Department of Chemistry and Biochemistry, TCU Box 298860, Texas Christian University, Fort Worth, TX 76129, USA.
Abstract:
In connection with a project aiming at the evaluation of antimicrobial agents, a vinyl phosphonate inhibitor of 3-dehydroquinate synthase was needed. As a result, the original five-step synthesis was reinvestigated resulting in a four-step process with some improved yields and three steps not requiring chromatographic purification. The overall yield was improved from 25% to 52%. However, despite significant efforts, the key olefination step could not be improved.
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