Structure elucidation, biogenesis, and bioactivities of acylphloroglucinol-derived meroterpenoid enantiomers from Dryopteris crassirhizoma.

Eighteen novel acylphloroglucinol meroterpenoid enantiomers were isolated from the rhizomes of Dryopteris crassirhizoma. Anti-inflammatory, antiviral, and antifungal activities were assessed. The anti-inflammatory mechanism of compounds 13 and 14 were investigated. [Display omitted] • Eighteen novel acylphloroglucinol meroterpenoid enantiomers were isolated from Dryopteris crassirhizoma and the stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. • Two intriguing methods were introduced to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds. • Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1β, and IL-18; their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. • A non-enzymatic biosynthesis of all meroterpenoids was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (± 1 /± 2) and chiral HPLC analyses. • Antiviral and antifungal activities were assessed. Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 ∼ 10 , 13 , 14 , and 17 ∼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 ∼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (± 1 /± 2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1β, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1). [ABSTRACT FROM AUTHOR]