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 beta-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.+image

Automated summary

This report describes the first total synthesis of Balgacyclamide B using a 17-steps pathway and achieving a 2% overall yield. The synthetic pathway can be adapted for the synthesis of Balgacyclamide A and C. The importance of cyclization conditions in converting or retaining configuration of beta-hydroxy amides via dehydrative cyclization is emphasized. The synthetic pathway provides a new route for the recently isolated cyanobactin's and can be used to explore porin-mediated transportation in gram-negative bacteria.