Total synthesis of pamamycin-649B.
The first total synthesis of the macrodiolide antibiotic pamamycin-649B (1) was achieved by using sultone methodology. The diethyl substituted larger hydroxy acid fragment was constructed in a concise fashion through domino elimination/alkoxide-directed 1,6-additions of ethyllithium to sultones derived from intramolecular Diels-Alder reaction of furan-containing vinylsulfonates. Intermolecular Yamaguchi esterification of the two hydroxy acid building blocks and subsequent Yamaguchi cyclization eventually provided the target macrocycle 1. Since the final lactonization with formation of the ester linkage between C1' and the C8 oxygen proceeded with complete C2' epimerization, the more readily available C2' epimeric smaller fragment could be used to streamline the synthetic sequence.
Fachrichtung Chemie und Lebensmittelchemie, Organische Chemie I, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany.
Petra
P
Fischer
Margit
M
Gruner
Anne
A
Jäger
Olga
O
Kataeva
Peter
P
Metz
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D003500:Cyclization; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D018942:Macrolides; C570943:pamamycin-649B; C024500:pamamycin