The stereoselective construction of small molecule mimics of biological structures is a key contribution organic chemistry can make to the discovery of new pharmaceuticals. We showed that peptide acetals could be efficiently 'zipped' up to generate single diastereomers of structurally diverse scaffolds, some of which showed exceptional ability to mimic type II beta-turns. We used the same chemistry in the solid phase synthesis of the important anthelmintic praziquantel.

An interesting class of compounds, what we term the 'enediamides', could be isolated from these pathways with suitable choice of reaction conditions; these enadiamides are formed from rearrangement of the first-formed acyliminium ion. They show interesting chemical properties, and it is possible to perform stereoselective chemical transformations on the double bond, directed by the amino acid stereocentre, and the electronically unsymmetrical nature of the double bond. We are exploring this, and related chemistry.

In a separate project, we synthesised novel peptidomimetic compounds based on quinazolinones as angiotensin II AT1 receptor antagonists. Through use of an advanced pharmacophore model, we were able to synthesise only 8 compounds and identify a molecule with biological activity in vivo superior to the market-leading drug, Losartan.