Stephen Swanson

A Mild and Regioselective Route to Functionalized Quinazolines

A Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4-aminoquinazolines in high yield. The method features a remarkably mild C(sp(2) )H activation step and can be exploited to rapidly access compounds with established biological activity.

Synthesis of Functionalized Pyridines via a Regioselective Oxazoline Promoted C–H Amidation Reaction

The first Rh-catalyzed C-H amidation of pyridines is reported. The incorporation of a substituent at the C2 position both is crucial to the success of this transformation and provides considerable scope for further elaboration of the resulting products. Among these compounds, 2-chloropyridines allow access to a selection of intermediates including a versatile azaquinazoline scaffold.

2-Iodoisatogens: Versatile Intermediates for the Synthesis of Nitrogen Heterocycles

A Cu-promoted cyclization of 2-nitrophenyl iodoacetylenes provides a direct route to a range of 2-iodoisatogens. These compounds represent useful intermediates for the late-stage elaboration of the C-I bond to furnish isatins and a range of alternative heterocyclic products.

A practical drug discovery project at the undergraduate level.

In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kδ) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. In total, 48 target compounds were prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and ≥tenfold, respectively.