An organocatalytic asymmetric approach to chiral proline derived diketopiperazines related to the prenylated indole alkaloid family

The prenylated indole alkaloids are a large family of natural products that have been isolated from various marine and terrestrial strains of Penicillium, Aspergillus and Malbranchea fungi. These compounds possess complex polycyclic structures including a characteristic bicyclo[2.2.2]diazaoctane core and have displayed wide-ranging biological activities. Chapter 1 gives an introduction to the prenylated indole alkaloids and important synthetic strategies to the key bicyclic core and an overview of previous work from our research group in this area. Recent work showed that triketopiperazines will undergo highly enantioselective Michael-additions and Michael addition–ring-closure reactions, efficiently generating compounds possessing the bicyclo[2.2.2]diazaoctane core found in the natural products. Chapter 2 discusses the extension of previous methodology towards a bicyclic triketopiperazine derived from proline including its synthesis and successful implementation in asymmetric Michael additions. Chapter 3 then explores the Michael addition–ring-closure of the proline derived triketopiperazine which was found to give highly enantioselective and high yielding access to hydroxy diketopiperazines possessing the key bicyclo[2.2.2]diazaoctane. The chapter also contains further transformations towards the natural product scaffold including a radical Barton-McCombie deoxygenation. Chapter 4 focusses on a novel Michael–Michael cascade strategy for the synthesis of molecules possessing the bicyclo[2.2.2]diazaoctane core of the prenylated indole alkaloids