1. Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck–Suzuki reaction
- Author
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Luca Laraia, Ashok R. Venkitaraman, Súil Collins, Warren R. J. D. Galloway, Brett M. Ibbeson, Esther Alza, Jamie E. Stokes, David R. Spring, Spring, David [0000-0001-7355-2824], and Apollo - University of Cambridge Repository
- Subjects
Scaffold ,34 Chemical Sciences ,biology ,Stereochemistry ,chemistry.chemical_element ,3405 Organic Chemistry ,General Chemistry ,Domino ,Tubulin ,Suzuki reaction ,chemistry ,Cell culture ,biology.protein ,Antimitotic Agent ,Human cancer ,Palladium - 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.
- Published
- 2015
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