Guanacastepene A 1 is a diterpene natural product, which showed excellent antibiotic activity against both Methicillin resistant <i>Straphylococcus aureus </i>(MRSA) and Vancomycin resistant <i>Enterococcus faecium </i>(VREF). The novel tricyclic structure and biological activity make it an excellent target for synthetic chemists, with over fifteen approaches reported in the literature to date. Our retrosynthetic analysis is based on the rearrangement of epoxy ketone 360, to afford the hydro-azulene core in a single transformation. Initial efforts on our racemic approach confirmed a photochemical rearrangement strategy as a suitable method for the synthesis of the natural product. A chiral variant, based on Jacobsen’s asymmetric conjugate addition, with malononitrile 366 afforded nitrile 395 in > 99% e.e. The serendipitous discovery of a diastereoselective nitrile reduction afforded the corresponding aldehyde, which was subjected to an intramolecular Barbier-Aldol annulation strategy to synthesise the key intermediate, hydro-naphthalene 380.

Extensive phytochemical studies carried out over the last two decades on plants of the genus <i>Illicium</i>, had led to the isolation and characterization of several anislactone-type sesquiterpenes. The neurotrophic activity of merrilactone A 17, coupled with the structural diversity which could be accessed by further derivatisation of other members, gives this family of secondary metabolites value in the process of discovering novel therapeutic agents to address the molecular causes underlying the progression of neurodegenerative diseases. Additionally, the anislactone-type sesquiterpenes family constitutes an ideal synthetic arena for the development of innovative methods dealing with the construction of highly-functionalised five-membered rings, and the creation of contiguous fully-substituted stereocentres. The thesis presented herein, describes the results obtained in the course of our investigations to lay the foundations of a synthetic program targeting the divergent total syntheses of several members of the anislactone-type sesquiterpenes family, including the novel implementation and limitations associated to a domino oxy-/carbopalladation reaction, which proved to be pivotal in the development of a short route towards the oxa[3.3.3]propellane carbocyclic core of merrilactone A, in addition to the development of a expeditive nine-steps route furnishing the tricyclic core of the anislactone-type sesquiterpenes 14, 15, 16 and 19, in a high overall yield.

The work described in this thesis has been primarily concerned with the synthesis of a number of different and novel chiral auxiliaries. All of the chosen synthetic routes to the desired auxiliaries utilised cheap and readily available terpenes from the "chiral pool". The utility of the successfully synthesised auxiliaries was evaluated in a range of asymmetric transformations, Lewis-acid catalysed Diels-Alder cycloadditions, 1,4-conjugate additions, boron enolate mediated aldol reactions and acylation reactions. The most successful auxiliaries were found to be two homologous camphor-based oxazolidin -2-one auxiliaries both of which were shown to impart excellent levels of asymmetric induction in all of the aforementioned reactions. In addition to chiral auxiliaries, some investigations were carried out on the development of camphor-derived chiral catalysts. The utility of these oxazaborolidine catalysts in asymmetric Diels-Alder cycloadditions and asymmetric ketone reduction reactions was then evaluated. It was found that neither catalyst imparted any stereoselectivity in the Diels-Alder reactions and only very low levels were observed in ketone reductions.

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