Syntheses of Anti-Phytopathogenic Fungal 2,7'-Cyclo-7,8'-neolignan-Type Indanes and Preparation of 8'-Epimer.

Abstract

The anti-phytopathogenic fungal activities against Alternaria alternata (Japanese pear) pathotypes of (-)- and (+)-γ-diisoeugenol, which have (7S,7'S,8'S)- and (7R,7'R,8'R)-2,7'-cyclo-7,8'-neolignan-type indanes, respectively, are compared herein with the stereoisomers of 7,8'-epoxy-8,7'-neolignan, which have tetrahydrofuran structures. The results highlight the advantages of (7S,7'S,8'S)-2,7'-cyclo-7,8'-neolignan, (-)-γ-diisoeugenol. A series of derivatives with effective absolute configurations were synthesized with high stereoselectivity via intramolecular Friedel-Crafts reactions, and biological assays were performed. The most effective compound identified in this research was the (4-OCH₃, 5-OCH₃, 3'-CF₃, 4'-OH)-derivative (EC₅₀ = 8.6 μM). The combination of a hydrophobic group at the 3'-position and a phenolic hydroxy group at the 4'-position was crucial for the high activity. The 8'-epimer of the effective (7S,7'S,8'S)-2,7'-cyclo-7,8'-neolignan compound was also prepared by stereoselective hydrogenation of the 7-8' internal alkene. Thus, a novel anti-phytopathogenic fungal 2,7'-cyclo-7,8'-neolignan-type indane was developed.