...................................................................................................................................... ii Acknowledgements .................................................................................................................... iv Abbreviations ........................................................................................................................... viii CHAPTER ONE: INTRODUCTION 1.1 Cancer in Modern Society ...................... ................................................................................3 1.1.1 Cancer Therapy: Targeting the Cell Cycle .. ..... ......................................................3 1.2 Paecilospirone – Isolation, Structure and Bios ynthesis ......................................... ...............5 1.3 Previous Syntheses Related to Paecilospirone ......................................................................7 A Clark-Lewis and McGarry ...................................................................................7 B Pettus and co-workers ......................... ...............................................................7 1.4 Aim of the Present Research ................. ................................................................................8 1.5 The Chemistry of Asymmetric Aldol Reactions ... ... ...........................................................9 1.5.1 Asymmetric Induction From the Aldehyde ..... . .................................................. 11 1.5.2 Asymmetric Induction From the Enolate ........................................................... 13 A Substrate-Mediated Aldol Reactions ........... ................................................... 13 B Auxiliary-Mediated Aldol Reactions ........... .................................................. 14 C Ligand-Mediated Aldol Reactions ........................................................... 17 1.5.3 Asymmetric Induction From a Chiral Lewis Aci d .................................................. 18 1.6 Retrosynthesis of Aldehyde Fragment 11 ............................................................................ 21 CHAPTER TWO: DISCUSSION 2.1 Synthesis of Spiroacetals 114 and 115 via an Acid-Catalysed Spirocyclisation Approach ...... 25 2.1.1 Overview ................................... .............................................................................. 25 2.1.2 Synthesis of Aldehyde 68 ........................................................................................ 26 2.1.3 Synthesis of Chiral Imide 48 .................................................................................. 29 2.1.4 Synthesis of Aldehyde 96 ........................................................................................ 30 A Using a Lewis Acid-Mediated Aldol Reaction .... . ...................................... 30 B Using a Magnesium Chloride-Catalysed anti-Aldol Reaction ........................ 32 C Using a Lactate-Derived anti-Aldol Reaction ............................................ 35 2.1.5 Synthesis of Bromide 99 ......................................................................................... 38