One of the most common methods for the synthesis of cyclic peptides is macrocyclization through amide coupling. Therefore, an attempt was made to construct the highly strained atrop-Tyr-Trp linkage in 15 through macrocyclization via amide coupling in the context of the total synthesis of micitide 982 (1) (Figure ). Compounds 13 and 14 were synthesized as precursors for cyclization, and various representative amide coupling reagents were screened. As a result, compound 15 derived from 13 was not observed under the conditions employing EDCI, DCC, DMTMM, PyBOP, HATU, or COMU. Even when using compound 14, compound 15 was not observed under the conditions employing EDCI, DCC, DMTMM, or PyBOP. Further screening revealed that while trace amounts of 15 were detected using compound 14 under the conditions employing HATU or COMU, the yield was significantly low (<5%). From these results, it became evident that the synthesis of atrop-Tyr-Trp linkage 15 through macrocyclization via amide coupling is challenging due to its significant strain.