Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase

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.