Syntheses of cerulenin and its analogs. II. Synthesis and biological activity of dl-carbacerulenin, a carbocyclic analog of cerulenin.
2,3-Epoxy-4-hydroxy-4-((E,E)-3,6-octadienyl)cyclopentanone (dl-carbacerulenin 5) was synthesized via the epoxyketones 15a and 15b as a mimic of the active form of the antibiotics cerulenin 1, a potent inhibitor of fatty acid synthetase (FAS). The monobenzyl ethers (12 and 13), synthetic intermediates of 15, were prepared by direct benzylation of the epoxycyclopentene (7). Inhibitory activity of synthesized 5 toward yeast FAS was less than that of cerulenin by a factor of 1000.
Shimazawa
R
R
Institute of Applied Microbiology, University of Tokyo, Japan.
Ogawa
Y
Y
Morisaki
N
N
Funabashi
H
H
Kawaguchi
A
A
Iwasaki
S
S
D002569:Cerulenin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002108:Ceruletide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
C079024:carbacerulenin; D002569:Cerulenin; D002108:Ceruletide; D064429:Fatty Acid Synthases