To piperidines and beyond

Thesis

This thesis describes the development of synthetic routes to investigate the relative and absolute stereochemistry of a number of piperidine alkaloids isolated from Microcos Paniculata. This thesis then goes on to explore an intramolecular Diels-Alder reaction, and explores its applicability to natural product synthesis.

Chapter 1 introduces the biological significance of piperidine alkaloids, followed by a brief review of noteworthy chemical syntheses of piperidine and (piperidine-containing) natural products.

Chapter 2 describes the isolation of Microcosamine A, and previous synthetic efforts towards the alkaloid. The chapter then describes the development and optimisation of a synthetic route to the alkaloid, culminating with independent verification of its relative and absolute configuration.

Chapter 3 describes the isolation, synthesis, and independent assessment of relative and absolute configuration of Microgrewiapines AꟷC, natural products from Microcos Paniculata.

Chapter 4 presents corrected 1H NMR data for the originally isolated sample of the alkaloid microconine. The asymmetric synthesis of the two C(3) epimeric forms of this compound are presented which allow the unambiguous assignment of relative and absolute configuration.

Chapter 5 describes the exploration of an intramolecular Diels Alder reaction using substrates derived from the amine ring opening of benzene oxide. Initial experiments use N-substituted allyl amines, which perform a ring opening and spontaneous cycloaddition in 1 step to yield racemic tricycles. Later an enantiopure route is developed utilising ring opening with a chiral amine.

Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2–5.

Authors: Taylor, CE

• DOI: 10.5287/ora-do86r2gbv
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English