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.