Flow photochemical routes to indoles and 8-membered lactones, and their application in target synthesis

Abstract

This thesis describes studies of two novel photochemical reactions towards 8-ring lactones and indoles, and the application of these products in target synthesis. Building on work by Bütenschon et al. and within the Harrowven group, the substrate scope of the photolysis of ninhydrin bis-acetals has been studied and expanded to the formation of 8-membered lactones. Meanwhile, the 8-membered lactone produced has been advanced to form cryptoacetalide, a natural component of the traditional Chinese medicine dan-shen, and a series of macrocycles which mirror the core structure of the resorcylic acid lactone family of natural products. This family exhibits a variety of biological activities and has been the subject of many natural product total syntheses which are reviewed herein. Furthermore, an oxidative flow photocyclisation of a variety of N-arylenaminones to indoles and carbozolones is described. Optimisations in respect to both yield and productivity are discussed in the context of a precursor to the WHO essential medicine, Ondansetron. These studies led us to design and develop novel experimental set-ups to conduct flow photochemical reactions at low temperatures and on large scales. Discussion of these reactors and their effectiveness is provided herein.

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Identifiers

ORCID for David Harrowven: orcid.org/0000-0001-6730-3573

ORCID for Richard Brown: orcid.org/0000-0003-0156-7087

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