Flavaglines are a class of natural products with potent insecticidal and anticancer activities. beta-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived beta-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent beta-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.
Lajkiewicz NJ, Cognetta AB, 3rd, Niphakis MJ, Cravatt BF, Porco JA, Jr. (2014) Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived beta-lactone Journal of the American Chemical Society136: 2659-64
Lajkiewicz NJ, Cognetta AB, 3rd, Niphakis MJ, Cravatt BF, Porco JA, Jr. (2014) Journal of the American Chemical Society136: 2659-64
