Synthesis of biologically active isoindolones via N-acyliminium ion cyclisations

Abstract

The preparation of diverse, architecturally complex molecules for pharmaceutical libraries represents a growing area of focus under the notion of diversity-oriented synthesis. Herein, we evaluate the use of N-acyliminium cyclisation reactions as a means for accessing privileged, natural product-like isoindolone structures. An excellent tolerance for various reagents and cyclisation conditions was observed, with the formation of various heterocyclic scaffolds achieved under straightforward reaction conditions and in good yields. This class of reaction was correspondingly used to synthesise a series of exploratory isoindolone derived compounds, for structure-activity testing as prospective treatments for colon cancer and leishmania (Biological hypothesis and data not supplied in this thesis due to confidentiality constraints with collaborators).