Synthesis and Investigation of the Abiotic Formation of Pyonitrins A–D

Pyonitrins A–D are recently isolated natural products from the insect-associated Pseudomonas protegens strain, which were isolated from complex fractions that exhibited antifungal activity via an in vivo murine candidiasis assay. Genomic studies of Pseudomonas protegens suggested that pyonitrins A–D are formed via a spontaneous nonenzymatic reaction between biosynthetic intermediates of two well-known natural products pyochelin and pyrrolnitrin. Herein we have accomplished the first biomimetic total synthesis of pyonitrins A–D in three steps and studied the nonenzymatic formation of the pyonitrins using 15N NMR spectroscopy.