Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived beta-lactone

Academic Article
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related to degree

  • Cognetta III, Armand B, Ph.D. in Chemical Biology, Scripps Research 2013 - 2018

publication date

  • February 2014

abstract

  • Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-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 β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.