The most challenging aspect in the total synthesis of micitide 982 (1) is the construction of the highly strained atrop-Tyr-Trp linkage. As mentioned earlier, obtaining the desired compound 15 was not possible under the conditions of intramolecular amide coupling due to excessive strain (Figure ). On the other hand, Larock macrocyclization is a bioorthogonal organic chemistry reaction that proceeds under mild conditions using Pd catalysts in the presence of an alkyne. It is known to be highly effective in the synthesis of macrocyclic peptides with significant strain. Therefore, applying Larock macrocyclization to compound 15 was expected to enable the construction of the desired highly strained atrop-Tyr-Trp linkage.