Studies towards the synthesis of Roseophilin

Lea, Louise (2001) Studies towards the synthesis of Roseophilin. PhD thesis, University of Glasgow.

Abstract

The pigment Roseophilin is a novel antibiotic with a topologically unique skeleton incorporating an ansa-bridged 1-azafulvene core and an extended conjugated heterocyclic chromophore comprising furan and pyrrole moieties. Chapter one discusses the nature of this and related products and summarises the major contributions made towards their synthesis. Chapter two discusses the possible approaches to this complex natural product and outlines the proposed research. The proposed macrocyclisation step, the Nicholas reaction, is reviewed in the following chapter.

The approach to the macrotricyclic core of Roseophilin is discussed in the ensuing chapters. Chapter four presents the initial strategy in which the [b]-fused pyrrole ring is constructed, by means of an aldol reaction onto a cyclopentanone frame.

A second strategy in which the [b]-fused pyrrole ring is approached via a 1,4-dicarbonyl compound, involving the synthesis and use of molybdenum electrophiles is discussed in chapter five.

A third and highly convergent strategy is presented in chapter six. This approach starts from pyrrole and makes use of the nucleophilicity of the heteroaromatic ring. The progress made in the approach to the macrotricyclic core is discussed. The building blocks for the isopropylsubstituted cyclopentanone ring are introduced via a Knoevenagel condensation 3-formylpyrrole and subsequent copper(I)-catalysed 1,4-addition. The reactive handle for the intramolecular macrocyclisation is introduced by a Sonogashira reaction at the 5-position of pyrrole. Finally the macrocyclisation studies, conclusions and perspectives are presented.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Kocienski, Prof. Philip
• Date of Award: 2001
• Depositing User: Angi Shields
• Unique ID: glathesis:2001-4513
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 06 Aug 2013 14:21
• Last Modified: 07 Aug 2013 10:21
• URI: https://theses.gla.ac.uk/id/eprint/4513