We report in this paper the first total synthesis of discobahamin A, a 24-membered macrocyclopeptide containing an alpha-keto amide functional group. We assign the absolute configuration of 2-hydroxy-3-methylpentanoic acid (Hmp), the side chain capping the N-terminus of the macrocycle, as the (2S, 3S) stereoisomer. A novel macrocyclization strategy was developed, utilizing an intramolecular Passerini reaction between omega-isocyano aldehyde and acetic acid. Notably, this macrocyclization proceeds via C(sp3)-C(sp2) bond formation and de novo generation of an alpha-keto amide functional group. Furthermore, we synthesized both the proposed structure of discobahamin B and its diastereomer. However, the spectroscopic data for these two compounds do not fully align with those reported for discobahamin B.