Improved Total Synthesis Of The Antitumor Romidepsin

The cyclic depsipeptide FK228 (previously named FR-901228) is a natural product histone deacetylase (HDAC) inhibitor which was isolated from the fermentation broth of Chromobacte-riumViolaceum, in 1991. FK228 have showed potent activity against a range of murine and solid tumor cells. Unrelated to the structural of other HDAC inhibitors, FK228 is a unique bicyclic depsipeptide.and a stable prodrug that becomes activated by the reduction of glutathione after uptake into cells. We report here a whole new strategically to preparing the key (4E,3S)-3-Hydroxy-7-mercapto-4-hepteno-ic acid. Devised nonaldol routes relying on the Grubbs 2nd Generation Catalyst. Avoid chromatographic separation of diastereomers. at the same time, An optimized way to Synthesis the key tripeptide is also described. We simplified experimental procedures, and improve yield of FK228.