Studies toward the asymmetric synthesis of (+)-dictyoxetane

Benford-Ward, Joseph (2022). Studies toward the asymmetric synthesis of (+)-dictyoxetane. University of Birmingham. Ph.D.

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Abstract

Dictyoxetane is a diterpene natural product isolated in 1985 along the coast of India, and it has not been found since. The structure consists of a trans-hydrindane unit, and the dioxatricyclic core which contains an oxetane moiety. There have been several publications demonstrating the synthesis of the dioxatricyclic core or similar structures, and a single report of the trans-hydrindane unit featuring a ketone for further elaboration. Despite this, the total synthesis of dictyoxetane has only been achieved once in the last 36 years, and as such further investigation is warranted. The literature surrounding dictyoxetane and methods to synthesise structurally similar fragments are critically reviewed in Chapter 1.

Chapter 2 contains studies toward the asymmetric synthesis of (+)-dictyoxetane via a cycloaddition approach, which require a key furan intermediate. The synthesis of this intermediate via haloformylation and enynol cyclisation-isomerisation is detailed. An investigation of the reviewed [4+3] and [4+2] cycloaddition methods to construct the oxabicyclo[3.2.1]octane base of the dioxatricyclic core was undertaken. One of the methods failed to yield an isolable oxabicycle, while the other three were either poorly selective or the resulting products could not be advanced toward (+)-dictyoxetane.

The final section of chapter 2 describes the use of a chiral auxiliary in a Diels-Alder reaction with the furan intermediate, resulting in a pair of regioisomeric oxanorbornenones. The ring-expansion of these strained ketones to the oxabicyclo[3.2.1]octane substructure is examined but remains inconclusive as a route to synthesising (+)-dictyoxetane.

Chapter 3 contains a conclusion of the work, and suggestions for further work should the project be continued past the work in this thesis. Chapter 4 details the experimental procedures and data for all compounds reported as part of the work. Chapter 5 contains all the cited references. Finally, following the references are the appendices, which contain all the characterisation data for synthesised compounds including NMR, MS, IR, and X-ray data.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):