Towards the total synthesis of Gelsemine

Aponte, Jennifer (2014). Towards the total synthesis of Gelsemine. University of Birmingham. Ph.D.

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Abstract

Discovered in 1870, in the roots of Gelsemium sempervirens, gelsemine has attracted the attention of numerous research groups over the years. Chapter 1 discusses the isolation and structure elucidation of this cage-like alkaloid, along with the synthetic strategies developed to assemble the densely functionalised hexacyclic skeleton.
An overview of the project and optimisation of the synthetic route to the gelsemine core structure are presented in Chapter 2. This sequence involves a 4+3 cycloaddition, a novel access to \(\alpha\) \(\beta\)-unsaturated esters and an elimination - Michael addition step. Finally, a shortened access to the gelsemine core structure from the key step is presented yielding sufficient material for further functionalisation studies.

Chapter 3 discusses two novel strategies towards the construction of the gelsemine spiro-oxindole from a key tricyclic ketone. A series of attempts at -arylation of ketones using haloacetanilide derivatives are described, culminating an unexpected one-pot indole synthesis. A spiro-oxindole synthesis is presented using a metal catalysed free-radical CH activation. Progress towards implementing this strategy on the gelsemine core structure is discussed.

In Chapter 4 the functionalisation of the bicyclo3.2.1octane core structure is discussed. Selective reduction of the tricyclic ketone gives an axial alcohol that cyclises to afford a lactone as the precursor of the tetrahydropyran ring.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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