Improved Total Synthesis of the Potent HDAC Inhibitor FK228 (FR-901228)
- 19 January 2008
- journal article
- letter
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 10 (4) , 613-616
- https://doi.org/10.1021/ol702957z
Abstract
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.Keywords
This publication has 18 references indexed in Scilit:
- The First Biologically Active Synthetic Analogues of FK228, the Depsipeptide Histone Deacetylase InhibitorJournal of Medicinal Chemistry, 2007
- Histone deacetylase inhibitor FK228 suppresses the Ras–MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanomaOncogene, 2005
- Total Synthesis of RK-397Journal of the American Chemical Society, 2005
- Histone deacetylase inhibitors – a new tool to treat cancerCancer Treatment Reviews, 2004
- Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase InhibitorJournal of the American Chemical Society, 2004
- Total Synthesis of the Depsipeptide FR-901375The Journal of Organic Chemistry, 2003
- IMDA-Radical Cyclization Approach to (+)-HimbacineOrganic Letters, 2003
- Asymmetric Samarium-Reformatsky Reaction of Chiral α-Bromoacetyl-2-oxazolidinones with AldehydesThe Journal of Organic Chemistry, 2000
- Asymmetric Transfer Hydrogenation of α, β-Acetylenic KetonesJournal of the American Chemical Society, 1997
- FR901228, a novel antitumor bicyclic depsipeptide produced by chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity.The Journal of Antibiotics, 1994