Total Synthesis of Chloptosin, a Potent Apoptosis-Inducing Cyclopeptide

A bidirectional total synthesis of chloptosin has been achieved in 16 operations (32 individual reactions) and 3% overall yield from the readily available materials. Palladium-catalyzed tryptophan synthesis, diastereoselective selenocyclization and oxidative deselenation successfully served as key steps in construction of the dimeric core amino acid. 2-Bromo-1-ethyl pyridinium tetrafluoroborate was efficiently employed in the peptide couplings with spatial encumbrance in this synthesis.