Towards the enantioselective total synthesis of luminacin D
Towards the enantioselective total synthesis of luminacin D
A proposed strategy for the enantioselective total synthesis of luminacin D, one of a family of 14 structurally similar compounds extracted from Streptomyces species which have been shown to possess anti-angiogenic properties, has been devised and tested. The luminacins are structurally similar, and for synthetic purposes are composed of an aromatic fragment linked to an aliphatic fragment.
The aromatic fragment has been synthesised in 5 steps from resorcinol in 19% overall yield. Acylation of resorcinol and subsequent reduction proceeds smoothly. The bismethoxymethyl protection was carried out in a two-step procedure. Optimal conditions for the hydroxymethylation reaction use 3 equivalents of s-butyl lithium and gave a 6:1 ratio of regioisomers. Protection of the resulting primary alcohol as a silyl ether proceeded smoothly. A trial coupling reaction of the aromatic fragment with 2.0 equivalents of acetaldehyde, 1.1 equivalents of s-butyllithium and tetramethylethylene diamine, provided the expected and desired racemic product in 77% yield.
Synthesis of the aldehyde fragment for the Nagao acetate-aldol reaction was carried out smoothly in 6 steps from propionaldehyde and methyl acrylate. Triethylsilyl protection gave 36% overall yield; p-methoxybenzyl protection gave 42% overall yield; an triisopropylsilyl protection gave 60% overall yield. The Nagao acetate aldol produced a single diastereoisomers in 67% yield when using triisopropylsilyl protection. With triethylsilyl protection, the Nagao product was isolated as a single diastereomer in 44% yield. With p-methoxybenzyl protection, the Nagao product was isolated as a mixture of diastereomers in 51% yield. Silyl protection of the Nagao product proceeded smoothly in 95% yield. Transformation to aldehyde for the Evans aldol reaction proceeded smoothly in 82% yield on a large scale.
University of Southampton
Gale, Helen
056e461a-0c2d-42c6-ad38-518e79a4824f
2005
Gale, Helen
056e461a-0c2d-42c6-ad38-518e79a4824f
Gale, Helen
(2005)
Towards the enantioselective total synthesis of luminacin D.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
A proposed strategy for the enantioselective total synthesis of luminacin D, one of a family of 14 structurally similar compounds extracted from Streptomyces species which have been shown to possess anti-angiogenic properties, has been devised and tested. The luminacins are structurally similar, and for synthetic purposes are composed of an aromatic fragment linked to an aliphatic fragment.
The aromatic fragment has been synthesised in 5 steps from resorcinol in 19% overall yield. Acylation of resorcinol and subsequent reduction proceeds smoothly. The bismethoxymethyl protection was carried out in a two-step procedure. Optimal conditions for the hydroxymethylation reaction use 3 equivalents of s-butyl lithium and gave a 6:1 ratio of regioisomers. Protection of the resulting primary alcohol as a silyl ether proceeded smoothly. A trial coupling reaction of the aromatic fragment with 2.0 equivalents of acetaldehyde, 1.1 equivalents of s-butyllithium and tetramethylethylene diamine, provided the expected and desired racemic product in 77% yield.
Synthesis of the aldehyde fragment for the Nagao acetate-aldol reaction was carried out smoothly in 6 steps from propionaldehyde and methyl acrylate. Triethylsilyl protection gave 36% overall yield; p-methoxybenzyl protection gave 42% overall yield; an triisopropylsilyl protection gave 60% overall yield. The Nagao acetate aldol produced a single diastereoisomers in 67% yield when using triisopropylsilyl protection. With triethylsilyl protection, the Nagao product was isolated as a single diastereomer in 44% yield. With p-methoxybenzyl protection, the Nagao product was isolated as a mixture of diastereomers in 51% yield. Silyl protection of the Nagao product proceeded smoothly in 95% yield. Transformation to aldehyde for the Evans aldol reaction proceeded smoothly in 82% yield on a large scale.
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Published date: 2005
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Local EPrints ID: 466738
URI: http://eprints.soton.ac.uk/id/eprint/466738
PURE UUID: 0f6362a3-f75a-4683-a612-7a16c4a118dd
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Date deposited: 05 Jul 2022 06:32
Last modified: 16 Mar 2024 20:51
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Author:
Helen Gale
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