Alkyl side-chain derivatives of sordaricin as potent antifungal agents against yeast.
Sordarin (1) was converted to 5 and 6, which showed potent antifungal activity against yeast. A series of C1-C9 alkyl side-chain derivatives was prepared, from which it was found that the optimal activity occurred with C5. A comparison of side chains with different unsaturation showed that the cis-alkene was the most active. This result suggested that the folding of the side chains might be crucial for the optimal activity.
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Dept of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Balkovec
J M
JM
Blazey
C M
CM
Hsu
M J
MJ
Nielsen
J
J
Schmatz
D
D
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004224:Diterpenes; D007192:Indenes; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D004224:Diterpenes; D007192:Indenes; D007202:Indicators and Reagents; C116705:sordaricin; C003329:sordarin