New Insights into Cyclobutenone Rearrangements: A Total Synthesis of the Natural ROS-Generating Anti-Cancer Agent Cribrostatin (ROS=reactive-oxygen species)

    Mubina Mohamed1, Théo P. Gonçalves1, Richard J. Whitby1, Helen F. Sneddon2, David C. Harrowven1

    • 1Dept of Chemistry, University of Southampton, UK
    • 2GSK Medicines Research Centre, Stevenage, UK

    Aryl- and heteroarylcyclobutenone rearrangements proceed in excellent yield under continuous-flow conditions. The former shows a Hammett correlation with σI providing strong evidence that electrocyclisation is the rate-determining step and has a late transition state. The reaction has been modelled by using DFT and CCSD(T) methods, with the latter giving excellent correlation with the experimental rate constant. A short and efficient total synthesis of cribrostatin 6, an anti-neoplastic and anti-microbial agent, provides a topical demonstration of the value of this method.

    Read the publication that featured this abstract

    Get in touch

    For more information on flow chemistry systems and services please use the contact methods below.

    Call us on +44 (0)1284 728659 or Email us