3-phenyl-5-methyl-2H,5H-furan-2-ones: Tuning antifungal activity by varying substituents on the phenyl ring

A series of racemic 3-phenyl-5-methyl-2H,5H-furan-2-ones related to a natur al product, (-)incrustoporine, was synthesized, and their antifungal activi ty evaluated. The key structural feature, furanone ring, was closed via H2S O4-mediated cyclization of 3-phenylpent-4-enoic acids. The compounds displa yed antifungal activity, especially against filamentous fungi. Expressed as the minimum inhibition concentration (MIC) in mu mol/L, the activity of th e most promising derivative against Absidia corymbifera matched that of ket oconazole (31.25 mu mol/L). In terms of mu g/mL, the substance was more act ive (7.6 mu g/mL) than this standard antifungal drug (16.6 mu g/mL). (C) 20 00 Elsevier Science Ltd. All rights reserved.