Synthesis and antifungal activity of novel 14-membered benzomacrolides, as galbonolide analogues.
Asymmetric total synthesis of benzene analogues of galbonolide, a 14-membered antifungal macrolide, possessing a benzene ring instead of a conjugated diene structure, was achieved starting from chiral 1-aryl-1-propanol obtained by enzyme-catalyzed kinetic resolution with high enantioselectivity. Representatively, a method for the introduction of a methylthio and chloride function at the vinyl position was also established. The resulting analogues unfortunately exhibited very little antifungal potency in comparison with galbonolide A.
Sakoh
Hiroki
H
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. sakouhk@banyu.co.jp
Sakuraba
Shunji
S
Sugimoto
Yuichi
Y
Imamura
Hideaki
H
Jona
Hideki
H
Yamada
Koji
K
Bamba-Nagano
Rie
R
Hashizume
Terutaka
T
Morishima
Hajime
H
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D005658:Fungi / Q000187:drug effects; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000935:Antifungal Agents; D007783:Lactones; D018942:Macrolides; C047784:rustmicin