title: New insights into cyclobutenone rearrangements: a total synthesis of the natural ROS-generating anti-cancer agent cribrostatin 6.
abstract: Aryl- and heteroarylcyclobutenone rearrangements proceed in excellent yield under continuous-flow conditions. The former shows a Hammett correlation with σ(I) 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.
authors.affiliation: Chemistry, University of Southampton, Highfield, Southampton, Hampshire, SO17 1BJ, UK.
authors.forename: Mubina
authors.initials: M
authors.lastname: Mohamed
authors.forename: Théo P
authors.initials: TP
authors.lastname: Gonçalves
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitby
authors.forename: Helen F
authors.initials: HF
authors.lastname: Sneddon
authors.forename: David C
authors.initials: DC
authors.lastname: Harrowven
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003503:Cyclobutanes / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D007546:Isoquinolines; D017382:Reactive Oxygen Species; C477578:cribrostatin 6; C553737:cyclobutenone