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).
Nicolaou
K C
KC
Department 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
Dethe
Dattatraya H
DH
Leung
Gulice Y C
GY
Zou
Bin
B
Chen
David Y-K
DY
D000081:Acetamides / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001393:Azoles / Q000737:chemistry; D006900:Hydroxylation; D018942:Macrolides / Q000737:chemistry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000081:Acetamides; D000900:Anti-Bacterial Agents; D001393:Azoles; C526942:GE2270C1; C520601:GE2270T; D018942:Macrolides; D010456:Peptides, Cyclic; D011725:Pyridines; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D010649:Phenylalanine; C030686:acetamide; C068122:GE 2270 A; C023666:pyridine