In the face of growing antibiotic resistance, the search for novel antibiotics has become a global health priority, specifically in regard to gram-negative bacteria, which possess an outer membrane that is highly resistant to penetration by most antibiotics. Darobactin A 4 (1, Figure ) and Dynobactin A (2, Figure ) are recently discovered natural products that show promising potent antibacterial properties against gram-negative pathogens, as well as low cytotoxicity. Adding further intrigue and promise to this class of antibiotics is its apparent ability to evade bacterial resistance through mutation. As such, the bactericidal activity of these natural products is of great interest and importance to the scientific community. Both 1 and 2 target BamA, a bacterial insertase within the BAM complex that facilitates folding and insertion of outer membrane proteins in gram-negative bacteria. However, 2, a decapeptide featuring two linked macrocycles, stands structurally distinct from its BamA-targeting counterpart 1. The unfused bicyclic structure possibly endows dynobactin A with flexibility and additional ionizable sites, resulting in a water solubility that exceeds that of 1 by more than 20-fold. The synthetic challenge posed by 1 was addressed concurrently last year by two separate groups. 17-18 2 encompasses several unique structural elements, including a C-C bond formed between C6 of the tryptophan residue and the b-carbon of the asparagine (C21), as well as a rare N-C linkage bridging the imidazole of histidine and b-carbon (C39) of the tyrosine unit. These intriguing structural complexities render 2 an exciting subject for synthetic pursuit. Yet, the intricate structure of 2 along with its natural scarcity pose a challenge to conventional (semi)synthetic approaches. This synthesis of 2 is concise considering its complexity, due to the recognition of a hidden strategic symmetry wherein parallel aziridine openings forge the challenging b-aryl disubstituted amino acids found in 2 prior to convergent assembly. In this Communication, the first total synthesis of 2 is disclosed, potentially enabling a deeper exploration of this promising natural product family.