Total synthesis of spiruchostatin A, a potent histone deacetylase inhibitor
Total synthesis of spiruchostatin A, a potent histone deacetylase inhibitor
The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the -hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.
chromobacterium-violaceum no-968, trichostatin-a, depsipeptide, fr901228
1030-1031
Yurek-George, Alexander
bf3e1ac0-1459-4c95-93da-d7adba966f39
Habens, Fay
3e4cce4b-4521-4702-9582-f817d25aad37
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9
2004
Yurek-George, Alexander
bf3e1ac0-1459-4c95-93da-d7adba966f39
Habens, Fay
3e4cce4b-4521-4702-9582-f817d25aad37
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9
Yurek-George, Alexander, Habens, Fay, Brimmell, Matthew, Packham, Graham and Ganesan, A.
(2004)
Total synthesis of spiruchostatin A, a potent histone deacetylase inhibitor.
Journal of the American Chemical Society, 126 (4), .
(doi:10.1021/ja039258q).
Abstract
The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the -hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.
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Published date: 2004
Keywords:
chromobacterium-violaceum no-968, trichostatin-a, depsipeptide, fr901228
Identifiers
Local EPrints ID: 26674
URI: http://eprints.soton.ac.uk/id/eprint/26674
ISSN: 0002-7863
PURE UUID: 8c639120-a591-4b64-b47e-19bfe4c09387
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Date deposited: 21 Apr 2006
Last modified: 16 Mar 2024 03:14
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Contributors
Author:
Alexander Yurek-George
Author:
Fay Habens
Author:
Matthew Brimmell
Author:
A. Ganesan
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