Enantiomeric Prenylated Neolignans from the Roots of Illicium verum with Analgesic Activity

Two pairs of unprecedented enantiomeric prenylated neolignans (1a/1b and 2a/2b) with an unparalleled 9.2′,8.O.3′-linked skeleton were isolated from the roots of Illicium verum, along with three biogenetically related metabolites (3a/3b and 4). The structures of these compounds were elucidated using spectroscopic techniques, X-ray crystallography analysis, and quantum chemical calculations. Both 2,4,5-trioxygenated phenylpropanoids (represented by 4) and their analogues with dearomatization of the benzene ring (represented by 3) are uncommon. Compounds 1a/1b and 2a/2b are likely produced by their dimerization. Inspired by the traditional effects of I. verum’s fruits, the analgesic activities of compounds 1–4 were evaluated using a glacial acetic acid-induced zebrafish pain model. The results indicated that all compounds showed different levels of analgesic activity. A major and active prenylated 2,4,5-trioxygenated phenylpropanoid with the dearomatization of the benzene ring (3) exhibited dose-dependent analgesic activity in a formalin-induced mouse paw licking assay. The analgesic potency of compound 3 is comparable to that of the positive drug diclofenac sodium (DCS) under the same dose (10 mg/kg). The analgesic potencies of compounds 3, 3a, and 3b were also comparable under a 2 mg/kg dose. The analgesic activities of prenylated phenylpropanoids with dearomatization of the benzene ring are first reported herein.