Total synthesis of thiostrepton. Assembly of key building blocks and completion of the synthesis.
The completion of the total synthesis of thiostrepton (1) is described. The synthesis proceeded from key building blocks 2-5, which were assembled into a growing substrate that finally led to the target molecule. Thus, the dehydropiperidine peptide core 2 was, after appropriate manipulation, coupled to the thiazoline-thiazole fragment 3, and the resulting product was advanced to intermediate 11 possessing the thiazoline-thiazole macrocycle. The bis-dehydroalanine tail equivalent 4 and the quinaldic acid fragment 5 were then sequentially incorporated, and the products so obtained were further elaborated to forge the second macrocycle of the molecule. Several roadblocks encountered along the way were systematically investigated and overcome, finally opening the way, through intermediates 20, 32, 44, 45, and 46, to the targeted natural product, 1.
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, CA 92037, USA.
Zak
Mark
M
Safina
Brian S
BS
Estrada
Anthony A
AA
Lee
Sang Hyup
SH
Nevalainen
Marta
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D008958:Models, Molecular; D013883:Thiostrepton / Q000138:chemical synthesis*
D000900:Anti-Bacterial Agents; D013883:Thiostrepton