The lack of new lead structures is a major obstacle in developing drugs for the treatment of bacterial infections. A promising yet under-investigated source for such compounds is ribosomally synthesized and posttranslationally modified peptides (RiPPs), a growing group of peptides mostly produced by microorganisms. Linear azole-containing peptides (LAPs), an important subgroup of RiPPs which include prominent natural products such as microcin B17 and goadsporin, are characterized by oxazoles and thiazoles derived from Ser/Thr and Cys via enzymatic cyclodehydration and dehydrogenation reactions. Recently, we extended the LAP family with plantazolicin A (1a) and B (1b) from the Gram-positive soil bacterium Bacillus amyloliquefaciens FZB42, which showed selective growth inhibition against nine Bacillus species (but not Staphylococcus or Enterococcus species), making it a new lead compound to fight Bacillus anthracis (anthrax) infections. However, fermentation only yielded minute amounts of 1a, hampering further studies on its mode of action, and its complex structure represents an attractive synthetic target. In this study, we present the first total synthesis of plantazolicin A (1a). Our synthetic route is designed to allow ready preparation of structural analogues for structure–activity relationship (SAR) studies through iterative couplings of precursor fragment peptides.