The enantioselective total synthesis of Sealutomicin C

Thesis

This thesis is divided into six chapters and concerns the successful total synthesis of the natural product sealutomicin C. Chapter 1 provides an overview of anthraquinone-fused enediyne natural products, the sealutomicin natural products, and other related cycloaromatised natural products. Chapter 1 also discusses prior work carried out in the Burton group by previous group member Dr Sean Guggiari towards the synthesis of the natural product unciaphenol, which bears structural similarities to sealutomicin C.

Chapter 2 details work undertaken to prepare lactone-fused chiral dihydroquinolines, using methodology developed by Dr Guggiari to construct the chiral dihydroquinoline scaffold. Chapter 3 discusses the use of these lactone-fused dihydroquinolines as substrates in a key organolithium mediated cyclisation to construct the core of enantiomeric sealutomicin C. Chapter 3 also discusses efforts to elaborate this core, resulting in the synthesis of tris-benzyl protected enantiomeric sealutomicin C.

Chapter 4 concerns the application of the chemistry developed in Chapters 2 and 3 to the synthesis of the correct enantiomer of sealutomicin C, culminating in a successful first-generation synthesis of the target natural product. Chapter 5 presents a shorter and more streamlined second-generation synthesis of sealutomicin C, improving on the work described in Chapters 2 – 4 by employing a more efficient protecting group strategy. Finally, Chapter 6 summarises our achievements and suggests potential strategies to apply the chemistry developed here to the synthesis of the structurally related natural products sealutomicins B and D.

Authors: Astle, S

• DOI: 10.5287/ora-dmkdd1pzj
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: sealutomicin; natural product synthesis; total synthesis
• Subjects: Chemistry, Organic