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CH activation and CH2 double activation of indolines: towards the synthesis of aspidospermidine and aspidofractinine

CH activation and CH2 double activation of indolines: towards the synthesis of aspidospermidine and aspidofractinine
CH activation and CH2 double activation of indolines: towards the synthesis of aspidospermidine and aspidofractinine
This thesis is concerned with the total synthesis of the two Aspidosperma alkaloid natural products, aspidospermidine and aspidofractinine. The two targets have a common pentacyclic molecular framework unique to this class of indole alkaloids.

Aspidospermidine has previously proven an attractive target, with over 20 total syntheses completed. The hexacyclic framework of aspidofractinine has proven more challenging, with only 5 total syntheses to date. These synthetic approaches are discussed in Chapter 1 together with the pharmacological activity exhibited within the Aspidosperma alkaloid series.

Chapter 3 details the challenges of installing the first 4 rings of the targets (the ABDE ring system). Ring expansion of a C3 cyclopropyl indolone with an imine, ultimately provided a quick and efficient route to the tetracyclic structure. With the model system realised, Chapter 3 details the synthetic efforts towards an elaborated imine component and its subsequent use in the ring expansion methodology to give our key precursor.

Chapter 4 discusses model systems to prove our key radical translocation step can be achieved. Systems are described that show intramolecular translocation of an aryl radical to C2 of an indoline is a feasible means of elaborating this centre.
Whiting, Sally
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Whiting, Sally
f8f08492-0bd1-4b16-9e6f-0d7d5bdf4444
Harrowven, David
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Whiting, Sally (2009) CH activation and CH2 double activation of indolines: towards the synthesis of aspidospermidine and aspidofractinine. University of Southampton, School of Chemistry, Doctoral Thesis, 247pp.

Record type: Thesis (Doctoral)

Abstract

This thesis is concerned with the total synthesis of the two Aspidosperma alkaloid natural products, aspidospermidine and aspidofractinine. The two targets have a common pentacyclic molecular framework unique to this class of indole alkaloids.

Aspidospermidine has previously proven an attractive target, with over 20 total syntheses completed. The hexacyclic framework of aspidofractinine has proven more challenging, with only 5 total syntheses to date. These synthetic approaches are discussed in Chapter 1 together with the pharmacological activity exhibited within the Aspidosperma alkaloid series.

Chapter 3 details the challenges of installing the first 4 rings of the targets (the ABDE ring system). Ring expansion of a C3 cyclopropyl indolone with an imine, ultimately provided a quick and efficient route to the tetracyclic structure. With the model system realised, Chapter 3 details the synthetic efforts towards an elaborated imine component and its subsequent use in the ring expansion methodology to give our key precursor.

Chapter 4 discusses model systems to prove our key radical translocation step can be achieved. Systems are described that show intramolecular translocation of an aryl radical to C2 of an indoline is a feasible means of elaborating this centre.

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Published date: 15 February 2009
Organisations: University of Southampton

Identifiers

Local EPrints ID: 71853
URI: http://eprints.soton.ac.uk/id/eprint/71853
PURE UUID: 8c8df8df-5f08-4f49-adcb-6944d2bd1ce4
ORCID for David Harrowven: ORCID iD orcid.org/0000-0001-6730-3573

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Date deposited: 06 Jan 2010
Last modified: 30 Jan 2020 01:27

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