Total Synthesis of Cyanobactin Natural Product Balgacyclamide B

Balgacyclamide A−C are a family of cyanobactin natural products isolated from freshwater cyanobacteria Microcystis aeruginosa. These macrocyclic peptides are characterized by their oxazoline‐thiazole core, their 7 or 8 stereocenters, and their antiparasitic activities. Balgacyclamide B is known for its activity towards Plasmodium falciparum chloroquine‐resistant strain K1, Trypanosoma brucei rhodesiense, and Leishmania donovani. In this report, the first total synthesis of Balgacyclamide B is described in a 17‐steps pathway and a 2 % overall yield. The synthetic pathway toward balgacyclamide B can be adapted for the future syntheses of balgacyclamide A and C. In addition, a brief history background of oxazolines syntheses is shown to emphasize the importance of the cyclization conditions used to interconvert or retain configuration of β‐hydroxy amides via dehydrative cyclization. A synthetic pathway for balgacyclamide B was developed in 17‐steps and a 2 % overall yield. The synthetic pathway opens a new route towards recently isolated cyanobactin's, especially for the balgacyclamide family and its analogs. Advanced intermediates from the synthetic pathway are being used to explore porin‐mediated transportation in gram‐negative bacteria.