Total synthesis of the thiopeptide promothiocin A

The thiopeptide (or thiostrepton) antibiotics are a class of sulfur-contain ing highly modified cyclic peptides with interesting biological activity. D escribed herein is the total synthesis of the thiopeptide antibiotic promot hiocin A, which utilizes a modified Bohlmann-Rahtz pyridine synthesis to es tablish the oxazolyl-thiazole-pyridine heterocyclic centerpiece of the anti biotic. The oxazole building blocks were obtained by a dirhodium(II)-cataly zed chemoselective carbenoid N-H insertion reaction followed by cyclodehydr ation, and the thiazoles by the Hantzsch reaction. Two different strategies for macrocyclization were successfully employed, with the dehydroalanine s ide chain of the natural product being introduced in the last steps of the synthesis.