Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction.
Ibbeson, Brett M
Stokes, Jamie E
Royal Society of Chemistry (RSC)
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Alza, E., Laraia, L., Ibbeson, B. M., Collins, S., Galloway, W., Stokes, J. E., Venkitaraman, A., & et al. (2015). Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction.. Chem Sci, 6 (1), 390-396. https://doi.org/10.1039/c4sc02547d
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.
Engineering and Physical Sciences Research Council (EP/J016012/1)
Royal Society (WM150022)
European Research Council (279337)
External DOI: https://doi.org/10.1039/c4sc02547d
This record's URL: https://www.repository.cam.ac.uk/handle/1810/271024
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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