Total Synthesis of the Cyclopeptide Alkaloid Abyssenine A. Application of Inter- and Intramolecular Copper-Mediated Coupling Reactions in Organic Synthesis

摘要

The first total synthesis of the 15-membered ring cyclopeptide alkaloid abyssenine A 1 has been achieved with a longest linear sequence of 15 steps. Central to the synthetic approach was an efficient copper-mediated Ullmann coupling/Claisen rearrangement sequence allowing for both ipso and ortho function-alization of aromatic iodide 4. This sequence was used for the synthesis of the aromatic core. The synthetic utility of copper-catalyzed coupling reactions was further demonstrated to install the enamide with a concomitant straightforward macrocyclization starting from acyclic α-amido-ω-vinyl iodide 13.