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The enantioselective synthesis of (-)-Luminacin D

The enantioselective synthesis of (-)-Luminacin D
The enantioselective synthesis of (-)-Luminacin D
Luminacin D, isolated from the fermentation broth of soil bacterium Streptomyces sp. Mer-VD1207, has angiogenesis inhibitory activity. In vivo studies have shown this activity derives from a novel mode of action, thus making luminacin D an interesting target for synthesis. Previous syntheses have not enabled the preparation of the spiro-epoxypyran moiety in a stereoselective manner, and luminacin D has been isolated as a mixture with the 6’,8’ – epimer as a result. This has been overcome by early, stereospecific introduction of the epoxide in our synthesis and we have constructed the natural product skeleton with the correct absolute stereochemistry, by chelation controlled diastereoselective additions. This has enabled possibly the first enantioselective and diastereoselective synthesis of this natural product to be completed. The allylation of ?-heteroatom substituted aldehydes was of significance to the synthesis as the key step in the synthesis involved allylation of an ?-epoxyaldehyde. These allylation reactions have been investigated by DFT calculations to unambiguously assign the Evans-Conforth and Polar Felkin-Ahn models in these additions.
Bartlett, Nathan
d0747614-b7a6-4856-b9ad-4367e13339e7
Bartlett, Nathan
d0747614-b7a6-4856-b9ad-4367e13339e7
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Bartlett, Nathan (2012) The enantioselective synthesis of (-)-Luminacin D. University of Southampton, Chemistry, Doctoral Thesis, 260pp.

Record type: Thesis (Doctoral)

Abstract

Luminacin D, isolated from the fermentation broth of soil bacterium Streptomyces sp. Mer-VD1207, has angiogenesis inhibitory activity. In vivo studies have shown this activity derives from a novel mode of action, thus making luminacin D an interesting target for synthesis. Previous syntheses have not enabled the preparation of the spiro-epoxypyran moiety in a stereoselective manner, and luminacin D has been isolated as a mixture with the 6’,8’ – epimer as a result. This has been overcome by early, stereospecific introduction of the epoxide in our synthesis and we have constructed the natural product skeleton with the correct absolute stereochemistry, by chelation controlled diastereoselective additions. This has enabled possibly the first enantioselective and diastereoselective synthesis of this natural product to be completed. The allylation of ?-heteroatom substituted aldehydes was of significance to the synthesis as the key step in the synthesis involved allylation of an ?-epoxyaldehyde. These allylation reactions have been investigated by DFT calculations to unambiguously assign the Evans-Conforth and Polar Felkin-Ahn models in these additions.

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Published date: 30 September 2012
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 354540
URI: https://eprints.soton.ac.uk/id/eprint/354540
PURE UUID: 611dd067-d89c-4a95-92c7-5cdb1fbeedcb
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

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Date deposited: 21 Oct 2013 12:37
Last modified: 06 Jun 2018 12:52

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