Total Synthesis of Micrococcin P1 through Scalable Thiazole Forming Reactions of Cysteine Derivatives and Nitriles
Mitchell P. Christy, Trevor Johnson, Clare McNerlin, John L. Woodard, Andrew Nelson, Bryant Lim, Tiffany L. Hamilton, Kaitlyn M. Freiberg, Dionicio Siegel
Abstract
Thiopeptides are a class of natural products with untapped therapeutic potential. To expand the methods available for the scaled production of these antibiotics, we report the laboratory synthesis of micrococcin P1 showcasing thiazole forming reactions of cysteine derivatives and nitriles followed by oxidation. In most instances, this thiazole forming sequence does not require chromatography and proved scalable. Using this approach, 199 mg of micrococcin P1 was generated in a single synthetic sequence.
Topics & Concepts
ThiazoleChemistryCombinatorial chemistrySequence (biology)CysteineOrganic chemistryBiochemistryEnzymeMicrobial Natural Products and BiosynthesisChemical Synthesis and AnalysisPeptidase Inhibition and Analysis