Total synthesis and anti-inflammatory evaluation of two prenylated coumestans.

Prenylated coumestans are structurally distinct natural products with potential anti-inflammatory activity. Herein, we report the total synthesis and biological evaluation of glytabastan B (1) and phaseol (2). The synthetic route featured efficient construction of the coumestan scaffold followed by regioselective prenylation through an Eu(fod)₃-catalyzed Claisen rearrangement, enabling the first total synthesis of glytabastan B (1) and access to regioisomer 21. In LPS-stimulated RAW264.7 macrophages, the diprenylated coumestans inhibited NO production at levels comparable to dexamethasone under the tested conditions, without apparent cytotoxicity. Preliminary structure-activity relationship analysis suggested that anti-inflammatory activity was mainly related to the number of prenyl groups, while their substitution position had only a minor effect. These findings provide synthetic access to bioactive prenylated coumestans and support further exploration of this scaffold as anti-inflammatory leads.