Studies towards the Total Synthesis of Phyllaemblic Acid

Kyle, Michael Patrick (2015). Studies towards the Total Synthesis of Phyllaemblic Acid. University of Birmingham. Ph.D.

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Abstract

Phyllaemblic acid is a spirocyclic acetal-containing natural product isolated from Phyllanthus emblica. A total synthesis of phyllaemblic acid has yet to be reported. The spirocyclic acetal portion of phyllaemblic acid is structurally similar to that found in the natural products phyllanthocin and breynolide. The introduction of this report discusses the literature methods used in the preparation of these spiroacetals, which might be applied in a synthesis of phyllaemblic acid.
Previous work in the Grainger group has approached the synthesis of phyllaemblic acid through disconnection to a meso 4-carbomethoxy-2,6-dihydroxy-substituted cyclohexanone, masked as a dioxabicyclononanone, prepared through an α,α’-annulation reaction of 2-substituted 1,3-dioxan-5-ones with methyl α-bromoacrylate. Epimerisation of the resulting ester gives the stereochemical array found in the carbocyclic ring of phyllaemblic acid.
This project attempted to address the current limitations of this approach, namely the lack of reactivity of the cyclohexanone carbonyl towards intermolecular nucleophilic addition reactions. An approach based on an intramolecular keto-alkyne cyclisation was first investigated, followed by the use of a Meyer-Schuster rearrangement to attempt to overcome the problems encountered in the conversion of the cyclohexanone to an enone. Finally, an approach to the perhydrobenzothiophene ring system found in breynolide using the meso 4-carbomethoxy-1,2-dihydroxy-substituted cyclohexanone was investigated.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):