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Updated: Jul 8, 2026

Production and Testing of Antimicrobial Peptides and Their Mimics
Published on: April 10, 2026
Total synthesis of thiopeptide antibiotics GE2270A, GE2270T, and GE2270C1
K C Nicolaou1, Dattatraya H Dethe, Gulice Y C Leung
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Abstract:
The total syntheses of the thiopeptide antibiotics GE2270A (7), GE2270T (8), and GE2270C1 (9) are described. The original synthetic strategies employed utilized the hetero-Diels-Alder reaction to construct the pyridine core of the target molecules and relied on a macrolactamization process to construct the macrocycle. The hetero-Diels-Alder-based strategy finally evolved allows the introduction of all four thiazole units attached to the pyridine ring and a one-pot sequence for macrocyclization and side-chain extension, culminating in highly convergent and expedient syntheses of these molecules as exemplified by a 24-step synthesis of GE2270C1 (9).
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