3,5-disubstituted pyranone analogues of highly antifungally active furanones: conversion of biological effect from antifungal to cytostatic.

A series of 3-aryl-5-acyloxymethyl-5,6-dihydro-2H-pyran-2-ones, related to highly antifungally active butenolides, was synthesized via cyclization of substituted δ-hydroxy acids as the key step, and evaluated for their in vitro antifungal activity and cytostatic activity. While the extension of the furanone ring to pyranone led to a complete loss of the antifungal effect, some of the compounds displayed promising effect against several cell lines, including the resistant colorectal carcinoma cells.

Neighboring group effect in Pd-catalyzed carbonylation terminated by lactonization: a need for a protective group and/or DMF.

Synthesis of analogues of antifungal podolactones via Pd-catalyzed processes revealed that tandem 6-exo-alkyne carbopalladation/carbonylative lactonization sequence is strongly solvent-dependent. Contrary to earlier reports, premature esterification was the predominant pathway when the starting enynes derived from (Z)-2-iodohex-2-en-1,4-diol were subjected to Pd-catalyzed carbonylation in MeOH. Apparently, irreversible complexation of Pd by the OH group prevented decarbonylation and hence 6-exo-alkyne carbopalladation. Similarly, the influence of the chelation was also evident when the reaction was applied to the analogous preparation of 3-hydroxymethylbutenolides. The neighboring group effect can be efficiently overcome through using DMF as the solvent in combination with protection of the OH function.

In vitro activities of 3-(halogenated phenyl)-5-acyloxymethyl- 2,5-dihydrofuran-2-ones against common and emerging yeasts and molds.

Three 3-(halogenated phenyl)-5-acyloxymethyl-2,5-dihydrofuran-2-ones were evaluated for activity against 191 strains of common and emerging yeasts and Aspergillus species by the broth microdilution test performed according to NCCLS guidelines. The furanone derivatives displayed broad-spectrum in vitro activity against potentially pathogenic yeasts and molds, especially Aspergillus spp. (MIC