Collect. Czech. Chem. Commun. 2007, 72, 1472-1498

Pentenolide Analogues of Antifungal Butenolides: Strategies Towards 3,6-Disubstituted Pyranones and Unexpected Loss of Biological Effect

Ivan Šnajdr, Jan Pavlík, Radan Schiller, Jiří Kuneš and Milan Pour*

Centre For New Antivirals and Antineoplastics, Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, Czech Republic


Pentenolide analogues of antifungal 3,5-disubstituted butenolides were prepared by oxidative cyclization of 2-(substituted aryl)hex-5-enoic acids as the key step. Given the limitations of the methodology, another approach to the title compounds based on the Pd-catalyzed carbonylative lactonization of 4-iodo-3-en-1-ols was developed, and the carbonylation conditions were optimized. While the former sequence allows only the introduction of a substituted methyl at C6, pyranones bearing a range of various C-substituents at C6 can be prepared by the latter. Somewhat surprisingly, unlike the corresponding butenolides with the same substitution pattern, the title pentenolides possess no antifungal or cytostatic activity.

Keywords: Pentenolides; Lactones; Electrophilic cyclization; Carbonylation; Stereoselective hydroalumination; Pd catalysis; Biological activity.

References: 41 live references.