C-20 oxidized furylethyl clerodane diterpenes isolated from Croton argyratus and their antifungal activity.

A thorough phytochemical study of a 50% MeOH/CH2Cl2 extract of Croton argyratus (Euphorbiaceae) yielded 17 furylethyl clerodanes, crotargyric acids A-L (1-12), ent-heteroscyphsic acids B, C, and F (13-15), crotargyrol (16), and biscrotargyric acid A (17). In these metabolites, the C-9 methyl group of the original clerodane scaffold was oxidized to a carboxylic acid in compounds 1-15 and 17 or to a hydroxymethyl in compound 16. Compounds 1-15 and 17 represent rare examples of clerodanes with a furylethyl moiety and a carboxylic acid at C-9. Other notable structural features include the A-ring rearranged cyclopentene in 1 and the ester-linkage in hetero-clerodane dimer 17, which is the first such example reported from Euphorbiaceae. The isolated compounds 5-12, 13-15, and 18-22 exhibited no cytotoxicity; however, 13 showed significant antifungal activity against Candida albicans, C. tropicalis, C. neoformans, and Rhizopus oryzae, with R. oryzae being the most sensitive species.