Dimeric alkenyl α-pyrones from Cryptocarya calcicola with their cytotoxicity.

The genus Cryptocarya is renowned for producing characteristic content of alkyl or alkenyl α-pyrones with intriguing stereochemical complexity and diverse pharmacological properties. In this study, four unprecedented dimeric alkenyl α-pyrones featuring an unusual pentacyclo[8.4.2.02,9.05,8.011,14]hexadecane core scaffold, named crypcalcones A-D (1-4), were isolated from Cryptocarya calcicola, an unexplored endemic Chinese species. Their structures were established through a combination of extensive NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism (ECD) spectroscopy. This is the first report of α-pyrone dimers from the genus Cryptocarya, expanding the known structural diversity of α-pyrones. Compounds 1-4 are proposed to arise from an initial 8π-6π e electrocyclization of a polyene α-pyrone precursor, followed by an intramolecular [4 + 2] cycloaddition. Notably, these compounds demonstrated selective cytotoxicity against HCT-116 colorectal cancer cells, with IC50 values ranging from 2.02 to 7.00 μM.