Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction

Esther Alza, Luca Laraia, Brett M. Ibbeson, Suil Collins, Warren R. J. D. Galloway, Jamie E. Stokes, Ashok R. Venkitaraman, David R. Spring

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed via domino Heck-Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.
Original languageEnglish
JournalChemical Science
Volume6
Issue number1
Pages (from-to)390-396
ISSN2041-6520
DOIs
Publication statusPublished - 2015
Externally publishedYes

Cite this

Alza, E., Laraia, L., Ibbeson, B. M., Collins, S., Galloway, W. R. J. D., Stokes, J. E., Venkitaraman, A. R., & Spring, D. R. (2015). Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction. Chemical Science, 6(1), 390-396. https://doi.org/10.1039/C4SC02547D