................................................................................................................................... vii CHAPTER 1 : INTRODUCTION ......................................................................................... 1 1.1 The pyranonaphthoquinone antibiotics ............................................................................... 3 1.2 The biological properties of pyranonaphthoquinone antibiotics ......................................... 5 1.3 Recent synthetic approaches to the pyranonaphthoquinone antibiotics .............................. 9 1.3.1 Electrophilic substitution .............................................................................................. 9 1.3.2 Electrophilic substitution and cyclization ................................................................... 11 1.3.2.1 Dotz benzannulation and oxa-Pictet-Spengler cyclization .................................. 11 1.3.2.2 Heck coupling and oxa-Pictet-Spengler cyclization ............................................ 24 1.3.3 Electrophilic cyclization ............................................................................................. 25 1.3.3.1 Asymmetric α-aminooxylation and oxa-Pictet-Spengler cyclization .................. 25 1.3.4 Electrophile-induced cyclization ................................................................................ 28 1.3.5 Organopalladium catalyzed cyclization ...................................................................... 34 1.3.6 Radical conjugate addition .......................................................................................... 40 1.3.7 Diels-Alder cycloaddition ........................................................................................... 43 1.3.8 Phthalide annulation ................................................................................................... 46 1.7.9 Toluate anion annulation ............................................................................................ 58 1.4 The dimeric pyranonapthoquinone antibiotic crisamicin A 18: isolation, biological properties and structure ..................................................................................................... 63 1.5 Aim of the present research ............................................................................................... 65 CHAPTER 2 : DISCUSSION ............................................................................................... 69 2.1 Overview ........................................................................................................................... 71 2.2 Synthesis of chiral (S,S)-enone 407 ................................................................................... 72 2.2.1 Attempted approach towards (S,S)-enone 407 ............................................................ 72 2.2.2 Revised synthetic route to (S,S)-enone 407 ................................................................ 77