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

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. KelloggJames A. Sikorski

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3206-3214
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number12
DOIs
StatePublished - 2017

Keywords

  • Cytotoxic activity
  • Marine natural products
  • Microtubule inhibitors
  • Pyrrole
  • Suzuki-Miyaura cross-coupling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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