Synthesis of the pyrrolidinone core of oxazolomycin A

Thesis

This thesis describes the development of synthetic strategies towards the densely functionalised pyrrolidinone core of the polyene β-lactone-γ-lactam antibiotic oxazolomycin A.

Chapter 1 The oxazolomycins

The oxazolomycins, a unique class of biologically active molecules containing a spiro-fused β-lactone-γ-lactam ring system are introduced. The isolation, structural elucidation and biological properties of the oxazolomycins as well as those of the structurally related inthomycins are reviewed.

Chapter 2 Previous syntheses

The two total syntheses of neooxazolomycin and the synthetic approaches to the pyrrolidinone core of oxazolomycin A and KSM-2690 B are evaluated.

Chapter 3 Project aims

An outline of the synthetic strategy employed in this project and details of the novel retrosynthesis of the pyrrolidinone core of oxazolomycin A are discussed.

Chapter 4 Synthetic studies towards the pyrrolidinone core of oxazolomycin A

The synthetic studies carried out towards the pyrrolidinone core of oxazolomycin A are described in detail. The preparation of an advanced intermediate containing the five chiral centres, four of which are contiguous, was achieved in twenty steps as a single diastereomer and as a single enantiomer.

Chapter 5 Synthetic studies towards the middle fragment of oxazolomycin A

A novel synthetic approach to the diene fragment contained in oxazolomycin A is reported. The formal synthesis of a dienyl iodide, in four fewer steps than previously reported was accomplished.

Chapter 6 Conclusions and future work

A summary of the synthetic work reported in this thesis and proposals for future study are presented.

Chapter 7 Experimental

Full experimental procedures and characterisation of compounds are reported.

Chapter 8 References

A complete list of citations employed in the previous seven chapters is provided.

Authors: O'Riordan, TJC

• Publication date: 2009
• DOI: 10.5287/ora-qmdmqbxb2
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Antibiotics; Natural products; Total synthesis
• Subjects: Organic synthesis; Synthetic organic chemistry; Natural products; Organic chemistry