Thomas Stephen Coulter

Chiral induction in cycloaddition reactions of azomethine ylides derived from secondary α-amino acids by the decarboxylative route

Abstract Cyclic secondary α-amino acids react with isatin and menthyl acrylate via decarboxylative azomethine ylide formation and subsequent cycloaddition involving an endo-transition state to give cycloadducts in 67-82% d.e. The stereochemistry of the major cycloadduct is assigned from a single crystal X-ray structure and a transition state model is proposed for the process.

Sequential 1,3-dipolar cycloaddition-palladium catalysed cyclisation. A powerful new tactical combination.

Abstract A new flexible tactical combination of a 1,3-dipolar cycloaddition of an in situ generated azomethine ylide followed by a palladium catalysed cyclisation is described. The two reactions can be carried out as a 1 pot procedure if desired. Four new stereocentres and two new rings are created by this strategy.

The synthesis and evaluation of indolylureas as PKCα inhibitors

PKCα and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKCα, but not PKA, are potential therapeutic targets for the treatment of heart disease. The synthesis of indolylureas are described, and a compound displaying nanomolar inhibition towards PKCα with significant selectivity over PKA has been identified.