Total synthesis of the antiviral glycolipid cycloviracin B.
The first total synthesis of the antiviral agent cycloviracin B1 (1) is described which provisionally establishes the hitherto unknown configuration of the chiral centers on the lateral fatty acid chains as (3R,19S,25R,3'R,17'S,23'R). Key steps en route to this glycolipid include a highly efficient template-directed macrodilactonization step for the formation of the lactide core followed by a two-directional synthesis strategy for the completion of the fatty acid annexes. The latter comprises a modified Julia-Kocienski olefination carried out in the presence of the base-labile beta-hydroxyester moieties of the macrodiolide, as well as a titanium-catalyzed asymmetric addition of the dialkylzinc reagent 11 controlled by cyclohexane-1,2-diamine bistriflate 12 for the formation of the chiral center at C-17' which is selectively glycosylated by taking recourse to the trichloroacetimidate method.
Fürstner
Alois
A
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany.
Mlynarski
Jacek
J
Albert
Martin
M
D039903:Actinobacteria / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D018942:Macrolides
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D018942:Macrolides; C077636:cycloviracin B1