Synthesis and late stage modifications of Cyl-derivatives

A peptide Claisen rearrangement is used as key step to generate a tetrapeptide with a C -terminal double unsaturated side chain. Activation and cyclization give direct access to cyclopeptides related to naturally occurring histone deacetylases (HDAC) inhibitors Cyl-1 and Cyl-2. Late stage modifications on the unsaturated amino acid side chain allow the introduction of functionalities which might coordinate to metal ions in the active center of metalloproteins, such as histone deacetylases.