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Towards the synthesis of marine natural products and their analogues by exploiting the Moore rearrangement

Towards the synthesis of marine natural products and their analogues by exploiting the Moore rearrangement
Towards the synthesis of marine natural products and their analogues by exploiting the Moore rearrangement
Since its development in the 1980s, the Moore rearrangement has become a powerful and versatile tool in synthetic chemistry.1 Mainly exploited in the synthesis of quinones, it can be used to access complex structures by careful manipulation of the reaction conditions. Herein is discussed its application in the synthesis of analogues of the natural product cribrostatin 6, as well as towards the first total synthesis of the pyrroloacridine alpkinidine.

Cribrostatin 6, isolated in 2003, has been shown to be active against seven cancer cell lines.2 Following the procedure developed by Harrowven et al.,3 cribrostatin 6 along with ten analogues were prepared for screening against the cancer cell line MCF-7. The results have shown the quinone unit to be amenable to change, with trends apparent in the cytotoxicity of these related compounds with respect to the nature of the substituents at position 8 and 9 on the cribrostatin 6 skeleton, their steric bulk and electronic properties. Further work is required to confirm these preliminary results in conjunction with exploring the effects of modifying the imidazopyridine unit.

With alpkinidine, synthetic work has looked to exploit this ring expansion in order to generate part of the fused pentacyclic ring system of this target natural product. Despite setbacks encountered along the way, the assembly of three of the five rings was achieved. Unfortunately, an inability to initiate the cascade of reactions required to furnish the last two rings of this acridine system halted progress towards alpkinidine. Although the target system could not be reached with the initial route developed, the Moore rearrangement still represents an interesting means of establishing part of this pyrroloacridine system.Should this prove not feasible, an alternative route based around an isoquinoline core has also been proposed.
Radigois, Marc
f02d8c16-d59c-4b6b-9b2c-bee54a3a1fcd
Radigois, Marc
f02d8c16-d59c-4b6b-9b2c-bee54a3a1fcd
Harrowven, David
bddcfab6-dbde-49df-aec2-42abbcf5d10b

Radigois, Marc (2016) Towards the synthesis of marine natural products and their analogues by exploiting the Moore rearrangement. University of Southampton, School of Chemistry, Doctoral Thesis, 139pp.

Record type: Thesis (Doctoral)

Abstract

Since its development in the 1980s, the Moore rearrangement has become a powerful and versatile tool in synthetic chemistry.1 Mainly exploited in the synthesis of quinones, it can be used to access complex structures by careful manipulation of the reaction conditions. Herein is discussed its application in the synthesis of analogues of the natural product cribrostatin 6, as well as towards the first total synthesis of the pyrroloacridine alpkinidine.

Cribrostatin 6, isolated in 2003, has been shown to be active against seven cancer cell lines.2 Following the procedure developed by Harrowven et al.,3 cribrostatin 6 along with ten analogues were prepared for screening against the cancer cell line MCF-7. The results have shown the quinone unit to be amenable to change, with trends apparent in the cytotoxicity of these related compounds with respect to the nature of the substituents at position 8 and 9 on the cribrostatin 6 skeleton, their steric bulk and electronic properties. Further work is required to confirm these preliminary results in conjunction with exploring the effects of modifying the imidazopyridine unit.

With alpkinidine, synthetic work has looked to exploit this ring expansion in order to generate part of the fused pentacyclic ring system of this target natural product. Despite setbacks encountered along the way, the assembly of three of the five rings was achieved. Unfortunately, an inability to initiate the cascade of reactions required to furnish the last two rings of this acridine system halted progress towards alpkinidine. Although the target system could not be reached with the initial route developed, the Moore rearrangement still represents an interesting means of establishing part of this pyrroloacridine system.Should this prove not feasible, an alternative route based around an isoquinoline core has also been proposed.

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Published date: February 2016
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 403848
URI: http://eprints.soton.ac.uk/id/eprint/403848
PURE UUID: 6274bfe3-663b-4831-91ef-dcdc77156d90
ORCID for David Harrowven: ORCID iD orcid.org/0000-0001-6730-3573

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Date deposited: 14 Dec 2016 15:39
Last modified: 24 Oct 2019 04:01

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Contributors

Author: Marc Radigois
Thesis advisor: David Harrowven ORCID iD

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