Improved Total Synthesis of the Potent HDAC Inhibitor FK228 (FR-901228)

A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key β-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydrox...

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Bibliographic Details
Published inOrganic letters Vol. 10; no. 4; pp. 613 - 616
Main Authors Greshock, Thomas J, Johns, Deidre M, Noguchi, Yasuo, Williams, Robert M
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 21.02.2008
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Depsipeptides - chemical synthesis
Depsipeptides - chemistry
Depsipeptides - pharmacology
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Histone Deacetylase Inhibitors
Molecular Structure
Physical Sciences
Science & Technology
DEPSIPEPTIDE
SPIRUCHOSTATIN-A
KETONES
HISTONE DEACETYLASE INHIBITOR
CHROMOBACTERIUM-VIOLACEUM NO-968
FR901228
TUMORS
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Summary:A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key β-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.
Bibliography:Medline
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ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1523-7060
1523-7052
DOI:10.1021/ol702957z