Chiral indanones and their derivatives

This thesis begins with an introduction to inflammation and the role of cell signalling and adhesion molecules within the body, drawing particular attention to the function of integrins and their ligands. Chapter 1 discusses the importance of the α4-integrin / paxillin interaction for α4β1-dependent cell migration and the recruitment of leukocytes. Herein, literature research into the identification of a racemic, non-cytotoxic molecule that inhibits this interaction is discussed, concluding with synthetic approaches towards the enantiomerically pure synthesis of this compound and its analogues. Chapter 2 opens with the discussion of some literature approaches to the synthesis of the indanone framework, followed by describing some initial synthetic work that was performed and the particular problems encountered with these methods. The attention of this chapter focuses on the kinetic resolution of indanones, applying both an enzymatic acylation and an oxidative kinetic resolution. The chapter demonstrates substrate viability in the aforementioned resolution techniques. Chapter 3 begins with discussing previous work in the synthesis of the target racemic compound. Following this, a detailed review of appropriate synthetic transformations is discussed, proceeding onto work towards the transformation of the enantiomerically enriched indanones into their corresponding quinolinones. The approach herein discusses some unanticipated results during this transformation