Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor
- 9 January 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (4) , 1030-1031
- https://doi.org/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 β-hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.Keywords
This publication has 6 references indexed in Scilit:
- Enantioselective Addition of a Chiral Thiazolidinethione-Derived Titanium Enolate to AcetalsOrganic Letters, 2001
- A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylasesProceedings of the National Academy of Sciences, 1998
- Synthesis of Natural and Modified Trapoxins, Useful Reagents for Exploring Histone Deacetylase FunctionJournal of the American Chemical Society, 1996
- FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination.The Journal of Antibiotics, 1994
- The Synthesis of Cystine Peptides by Iodine Oxidation of S‐Trityl‐cysteine and S‐Acetamidomethyl‐cysteine PeptidesHelvetica Chimica Acta, 1980
- A Rapid Esterification by Means of Mixed Anhydride and Its Application to Large-ring LactonizationBulletin of the Chemical Society of Japan, 1979