Total Synthesis of Thiopeptide Antibiotics GE2270A, GE2270T, and GE2270C1

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 ).