Scalable Synthesis of Thiazole Peptide Macrocycles

Synthesis of the 26-Membered Core of Thiopeptide Natural Products by Scalable Thiazole-Forming Reactions of Cysteine Derivatives and Nitrile: T. C. Johnson, M. P. Christy, D. Siegel

Synthesis 2021, 53, DOI: 10.1055/s-0040-1706478


Antibiotic-resistant bacteria represent an increasingly threatening issue for global health, due to the rapid and continuing emergence of novel resistance mechanisms combined with antibiotics being deprioritized in the drugs portfolio of pharmaceutical companies, a trend which has characterized the last three decades of drug development. Novel effective and resistance-free antibiotics are therefore dramatically needed to counter this emergency. Recently, the group of Professor Dionicio Siegel from the University of California San Diego (USA) reported a new synthetic approach to macrocyclic peptides incorporating thiazolyl amino acids, based on a cysteine/nitrile condensation reaction followed by oxidation to generate the target thiazole units.

Professor Siegel said: “Thiazolyl peptides represent a promising class of antibiotics for human use and toward this goal the pharmacophore of the 26-membered class of compounds has been synthesized on scales enabling future elaboration.”

Get Trial Access to the chemistry journals
Download SYNFORM or read it online