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 beta-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.
Greshock
Thomas J
TJ
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Johns
Deidre M
DM
Noguchi
Yasuo
Y
Williams
Robert M
RM
D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D015394:Molecular Structure
D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin