Ortho Group Activation of a Bromopyrrole Ester in Suzuki-Miyaura Cross-Coupling Reactions: Application to the Synthesis of New Microtubule Depolymerizing Agents with Potent Cytotoxic Activities

Publication date: Available online 11 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): John T. Gupton, Scott Yeudall, Nakul Telang, Megan Hoerrner, Ellis Huff, Evan Crawford, Katie Lounsbury, Michael Kimmel, William Curry, Andrew Harrison, Wen Juekun, Alex Shimozono, Joe Ortolani, Kristin Lescalleet, Jon Patteson, Veronica Moore-Stoll, Cristina C. Rohena, Susan L. Mooberry, Ahmad J. Obaidullah, Glen E. Kellogg, James A. Sikorski
New microtubule depolymerizing agents with potent cytotoxic activities have been prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The utilization of ortho activation of a bromopyrrole ester to facilitate successful Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic methodology. This strategy allows for control of regiochemistry with the attachment of four completely different groups at the 2, 3, 4 and 5 positions of the pyrrole scaffold. Biological evaluations and molecular modeling studies are reported for these examples.

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