The total synthesis of concavine

Saint-Dizier, François (2016). The total synthesis of concavine. University of Birmingham. Ph.D.

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Abstract

Concavine, a diterpene natural product was isolated from a strain of Clilocybe concava in 2005 and was the first diterpene alkaloid to be isolated from a mushroom. Chapter 1 presents the unprecedented core structure of this novel alkaloid consisting of a bicyclo(3.2.1 ]octane system linked with a oxazepane ring. Our retrosynthetic analysis highlighting the challenges for the synthesis of concavine is presented.
Chapter 2 discusses the formation of the bicyclo
[3.2.1]octane system and the installation of an oxazepane ring precursor. The different strategies used to form the five-membered ring and the regioselectivity issues surrounding the addition of the oxazepane ring precursor are discussed.
The completion of the core structure of concavine and the end game is described in Chapter 3. While the strategy to use a sulfone group as a ketone precursor was not successful, the hydrolysis of a vinyl sulfide group was key to access the desired ketone and complete the total synthesis of concavine.
In Chapter 4 the comparison between the reported data for concavine and our synthesised compound is described. The synthesis of a new epimer was undertaken to solve the mismatch in the data without success. Both the HCI and AcOH salts ofthe synthesised concavine were formed to investigate the impact of a protonated amine on the chemical shift compared to the free amine.
A summary of the total synthesis of concavine is presented in Chapter 5. The successful sequence for the formation of concavine from the commercially available anhydride and the work to match the data with the reported natural product is summarised.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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