17S,20S-Methanofusidic acid, a new potent semi-synthetic fusidane antibiotic.
A novel fusidic acid type antibiotic having the side chain linked to the tetracyclic ring system via a spiro-cyclopropane system is described. 17S,20S-Methanofusidic acid is obtained by an efficient synthetic route including cyclopropanation of the Delta17(20) bond with attack solely from the least hindered alpha-face. The spiro-cyclopropane system orients the side chain into a bioactive conformational space. The new 17S,20S-methanofusidic acid exerts antibacterial activity against several Gram-positive species with potency essentially equal to natural fusidic acid.
Duvold
Tore
T
LEO Pharma, Industriparken 55, DK-2750 Ballerup, Denmark. tore.duvold@leo-pharma.com
Jørgensen
Anne
A
Andersen
Niels R
NR
Henriksen
Anne S
AS
Dahl Sørensen
Morten
M
Björkling
Fredrik
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship
C475534:17,20-methanofusidic acid; D000900:Anti-Bacterial Agents; D005672:Fusidic Acid