Guaiane-type sesquiterpenoids with various ring skeletons from Daphne bholua uncovered by molecular networking and structural revisions of previously reported analogues

• Published in: Bioorganic chemistry 2022-12, Vol.129, p.106208-106208, Article 106208
• Main Authors: Dong, Shu-Hui, Duan, Zhi-Kang, Ai, Yun-Fei, Zhou, Xiao-Fang, Zhang, Xin, Lian, Mei-Ya, Huang, Xiao-Xiao, Bai, Ming, Song, Shao-Jiang
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase inhibitory activity; Daphne bholua; Guaiane-type sesquiterpenoids; Molecular networking; Structural revisions
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.106208

[Display omitted] •Twenty guaiane-type sesquiterpenoids were isolated from D. bholua with integrating molecular networking and Molnetenhancer.•The chemical structures and configurations of the isolates were established via extensive methods.•Two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised.•The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico. The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1–7) along with thirteen known analogues (8–20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke’s method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.