Zili Ren's research while affiliated with Northwest A & F University and other places

Osthole, a naturally occurring coumarin-type compound, is isolated from a Chinese herbal medicine Cnidium monnieri (L.), and exhibits a broad range of biological properties. In this review, the total synthesis and structural modifications of osthole and its analogs are described. Additionally, the progress on bioactivities of osthole and its analogs is outlined since 2016. Moreover, the structure-activity relationships and mechanisms of action of osthole and its derivatives are discussed. These can provide references for future design, development and application of osthole and its analogs as drugs or pesticides in the fields of medicine and agriculture.

Osthole, a coumarin-type natural product, is isolated from Chinese traditional herbal medicine Cnidium monnieri. In order to improve the pesticidal activity of osthole, and high value-added application of the plant Cnidium monnieri, a series of new derivatives containing hydrazone/acylhydrazone/sulfonylhydrazone skeletons at the C-8 position of osthole were regioselectively semi-prepared. The steric structure of 3c was determined by the X-ray crystal structure. Against Mythimna separata Walker, benzoylhydrazone 3b (R¹ = 4-CH3Ph) showed 1.6 folds potent insecticidal activity of the precursor osthole. Introduction of the acylhydrazones on the 3'-methyl-2'-butylenyl fragment at the C-8 position of osthole can improve the insecticidal activity. These will provide a foundation for future structural modifications of osthole as pesticidal agents.

BACKGROUND In order to discover natural‐product‐based pesticidal candidates, a series of coumarin‐like derivatives containing oxime ester fragments at the C‐8 position were prepared by structural modification of osthole, a natural plant product isolated from Cnidium monnieri. Their pesticidal activities were evaluated against two typically fruit trees/crop‐threatening agricultural pests, Mythimna separata Walker and Tetranychus cinnabarinus Boisduval. RESULTS Osthole was regioselectively oxidized by selenium dioxide to give the E‐isomer, (2′E)‐3′‐formaldehydylosthole (2). Four key steric structures of 2, (2'E, 4'E)‐(o‐chloropyrid‐3‐ylcarbonyl)oximinylosthole (4o), (2'E, 4'E)‐(styrylcarbonyl)oximinylosthole (4t), and (2'E, 4'E)‐(acetyl)oximinylosthole (4w) were undoubtedly confirmed by X‐ray crystallography. Against T. cinnabarinus, it is noteworthy that (2′E, 4′E)‐(p‐chlorophenylcarbonyl)oximinylosthole (4c) exhibited over three‐fold more potent acaricidal activity of the precursor osthole, with especially good control efficiency observed in the glasshouse. Against M. separata, compounds 4c and (2′E, 4′E)‐(p‐nitrophenylcarbonyl)oximinylosthole (4f) showed the most pronounced growth inhibitory activity. The relationships between their structures and agricultural activities also were studied. CONCLUSION These results demonstrate that compound 4c could be further structurally modified as pesticidal agents. It will lay the foundation for future application of osthole derivatives as pesticides. © 2020 Society of Chemical Industry