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New Insights into Cyclobutenone Rearrangements: A Total Synthesis of the Natural ROS‐Generating Anti‐Cancer Agent Cribrostatin 6
Author(s) -
Mohamed Mubina,
Gonçalves Théo P.,
Whitby Richard J.,
Sneddon Helen F.,
Harrowven David C.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102263
Subject(s) - yield (engineering) , chemistry , reaction rate constant , transition state theory , computational chemistry , thermodynamics , physics , quantum mechanics , kinetics
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.