Studies toward the total synthesis of phyllaemblic acid

Casey, Tyrone Christopher (2013). Studies toward the total synthesis of phyllaemblic acid. University of Birmingham. Ph.D.

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Abstract

Phyllaemblic acid is a highly oxygenated natural product isolated along with a number of related compounds from the roots of Phyllanthis emblica L. by Zhang et al. in 2000.
The roots of this shrub have been used by the people in south-east Asia as an antiscorbutic and in the treatment of diverse ailments, especially those associated with the digestive organs. A total synthesis has yet to be reported.

A concise sequence has been developed which rapidly furnishes a range of meso bridged bicyclic ketones, in good yield and with complete diastereocontrol, utilizing on an α,α’-annelation reaction of 1,3-dioxan-5-ones. The bicyclic systems are shown to adopt chair-boat conformations in both solution and in the solid state. Single
diastereomers are obtained in two cases with two different substituents. Stereochemical outcomes have been rationalized using steric and stereoelectronic arguments.

Carbon-carbon bond formation at the ketone carbonyl in these bicyclic systems is shown to be problematic. Ortho-acetal hydrolysis and diol reprotection as a bis-TBS ether provides a monocyclic system with increased ketone reactivity, allowing elaboration to an α-hydroxyaldehyde of appropriate stereochemistry for future application in a synthesis of the natural product. Preliminary studies towards this goal on a simplified model system are reported.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):