Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck–Suzuki reaction. Issue 1 (19th September 2014)

• Record Type: Journal Article
• Authors: Alza, Esther; Laraia, Luca; Ibbeson, Brett M.; Collins, Súil; Galloway, Warren R. J. D.; Stokes, Jamie E.; Venkitaraman, Ashok R.; Spring, David R.
• Is Part Of: Chemical science. Volume 6:Issue 1(2015:Jan.)
• Page Start: 390
• Page End: 396
• Publication Date: 2014-09-19
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c4sc02547d
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : The synthesis of a previously undescribed sp 3 -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported. Abstract : The synthesis of a previously undescribed sp 3 -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.