A concise and scalable total synthesis of dictyodendrin B by sequential C–H functionalisation

This thesis describes the total synthesis of the marine alkaloid dictyodendrin B (2). Our investigations were primarily directed towards achieving this goal via a sequential C–H functionalisation strategy (Scheme 1). The functionalisation of C–H bonds has attracted considerable interest due to its potential impact on the synthesis of complex molecules. Our aim was to demonstrate the advantages and feasibility of performing an extended sequence of C–H functionalisations to simplify and streamline the synthesis of a sufficiently challenging target. The dictyodendrins, a family of telomerase-inhibiting marine alkaloids that have been investigated for their anti-cancer properties, became the focus of our attention due to their dense functionalisation. Each dictyodendrin can be viewed as having a central indole core that is peripherally decorated with a large number of substituents. We envisaged that performing sequential C–H functionalisations on a simple unfunctionalised indole would provide an excellent platform to demonstrate our strategy. We were subsequently able to perform a sequence of reactions, including 5 C–H functionalisations, to afford dictyodendrin B (2) from the minimally functionalised and readily available 4-bromoindole (1). The complete functionalisation of the indole was performed on gram-scale and enabled rapid construction of this complex natural product in a highly concise manner.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2015

Author dc:creator

• Pitts, Andrew Keith

Advisor dc:contributor.advisor

• Gaunt, Matthew

• Dictyodendrin B
• C–H functionalisation

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d4d85aff-1e9e-47d7-b1aa-3625bd8cca12/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.93006

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/345586