The synthesis of the highly strained atrop-Trp-Trp linkage by macrocyclization of 11 is noteworthy in that the cyclization 14 is obtained with perfect atroposelectivity. The atroposelectivity of this reaction is addressed (Scheme 1). First, in the Larock macrocyclization of the cyclization precursor 11, Pd undergoes an oxidative addition to Ar-Br bond. Then, the 12 formed in the reaction system is subjected to a regioselective migratory insertion onto the neighboring triple bond, avoiding the TES group, to obtain 14 with the desired atrop-Trp-Trp linkage. On the other hand, 15 with undesired atrop-Trp-Trp linkage is not generated at all via 13. This is probably due to the energetic disadvantage of the process via 13 in the transition state of the reaction. To confirm the stability of the atrop-C-N bond of 14, 14 was heated in PhMe at 110 ºC for 8 h and 1H NMR experiment was performed. However, 15 was not observed and only 14 was recovered. The atrop-C-N bond of 14 was found to be thermodynamically stable. To complete the total synthesis of cihunamide B (1), only the conversion of benzyl ester 14 to the primary amide and the removal of the protecting groups remain. 14 obtained by Larock macrocyclization was derivatized to carboxylic acid 16 by hydrogenation in the presence of Pd/C. Subsequently, the amidation of 16 with NH3 was successfully carried out by HATU to afford 3.62 g of protected cihunamide 17. Finally, the protected cihunamide 17 was subjected to hydrolysis of the Me-ester, and the total synthesis of cihunamide B (1) was completed by deprotection of the Boc and TES groups with TFA.