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Towards the total synthesis of RP-66453

Towards the total synthesis of RP-66453
Towards the total synthesis of RP-66453
This thesis outlines synthetic work towards the total synthesis of RP-66453, a natural product isolated from a strain of Actinomycetes bacteria which has been shown to bind to the neurotensin antagonist of guinea pigs. The synthesis of several analogues of the biaryl ether macrocycle of RP-66453 have been completed via SNAr ring closure. Our approach employed chiral phase transfer catalyst methodology to synthesise unnatural a-amino acids, which allowed us to develop an efficient and concise route to an advanced intermediate on route to RP-66453.

Strategies to form the biaryl macrocycle of RP-66453 are also explored using a model substrate. This led us to modify our original strategy and consider using a phenanthrene intermediate as a surrogate of the A-B macrocycle. This could be formed by a radical or photochemically induced transannular ring contraction.
Twiddy, Scott
f3286a65-9c7e-438a-8a5b-4fe8711cd72d
Twiddy, Scott
f3286a65-9c7e-438a-8a5b-4fe8711cd72d
Harrowven, David
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(2012) Towards the total synthesis of RP-66453. University of Southampton, Chemistry, Doctoral Thesis, 228pp.

Record type: Thesis (Doctoral)

Abstract

This thesis outlines synthetic work towards the total synthesis of RP-66453, a natural product isolated from a strain of Actinomycetes bacteria which has been shown to bind to the neurotensin antagonist of guinea pigs. The synthesis of several analogues of the biaryl ether macrocycle of RP-66453 have been completed via SNAr ring closure. Our approach employed chiral phase transfer catalyst methodology to synthesise unnatural a-amino acids, which allowed us to develop an efficient and concise route to an advanced intermediate on route to RP-66453.

Strategies to form the biaryl macrocycle of RP-66453 are also explored using a model substrate. This led us to modify our original strategy and consider using a phenanthrene intermediate as a surrogate of the A-B macrocycle. This could be formed by a radical or photochemically induced transannular ring contraction.

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Published date: 31 October 2012
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 353099
URI: http://eprints.soton.ac.uk/id/eprint/353099
PURE UUID: f02a7dd4-c6fe-4bed-931b-0abe6dc57447
ORCID for David Harrowven: ORCID iD orcid.org/0000-0001-6730-3573

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Date deposited: 29 May 2013 13:28
Last modified: 14 Jul 2018 00:36

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