Progress towards the total synthesis of N-methylwelwitindolinone C isothiocyanate

Paulin, Cynthia Béatrice Julie (2013). Progress towards the total synthesis of N-methylwelwitindolinone C isothiocyanate. University of Birmingham. Ph.D.

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Abstract

This thesis focuses on our progress towards the total synthesis of N-methylwelwitindolinone C isothiocyanate 7, commonly called welwistatin. This major alkaloid of the welwitindolinone family, which was isolated from Hapalosiphon welwitschii in 1994, represents a particularly attractive target due to its interesting biological activities (MDR reversing agent) and its challenging structure. Welwistatin possesses a complex bicyclo[4.3.1]decane ring system consisting of four stereogenic centres, three quaternary carbons and two unusual reactive functionalities: the isothiocyanate bridgehead and a vinyl chloride group.

Inspired by the synthetic challenge of this complex architecture, the Simpkins group reported an expedient four-step synthesis of its core structure in 2005. Three years later, our group had investigated the reactivity at the bridgehead enolate positions. Taking inspiration from this previous work, we successfully synthesised bridgehead alkene 126. The other features present on welwistatin 7 were then investigated and enone 198 was obtained.

Facing some difficulties on the model system 88, we turned our attention towards the synthesis of tetracycle 170, possessing the gem-dimethyl at the position C\(_{16}\), and its subsequent functionalisation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):