Total Synthesis of Thiopeptide Antibiotics GE2270A, GE2270T, and GE2270C1

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).