Honolignols A–C, Three Racemic Forms of Honokiol-Derived Dimeric Neolignans from Magnolia Officinalis Var. Biloba

作者：Wei-Ming Huang, Ping Ying, Han-fei Gong, Yue-You Yang, Chuan-Lu Fu, Ze Liu, Zi-Wei Jia, Zhenzhen Zhang, Lingyi Kong, Wen‐Jun Xu · 发表于：The Journal of Organic Chemistry · 年份：2025 · DOI：10.1021/acs.joc.5c02184 · 被引用次数：5 · 研究领域：Magnolia and Illicium research、Plant-derived Lignans Synthesis and Bioactivity、Traditional and Medicinal Uses of Annonaceae

Three pairs of racemic honokiol-derived dimeric neolignans, named honolignols A–C ( 1 – 3 ), featuring unique carbon skeletons, were isolated from the barks of Magnolia officinalis var. biloba . Honolignol A ( 1 ) represents a novel polycyclic neolignan characterized by an unprecedented 3,13-dioxapentacyclo[10.4.1.0 2,10 .0 4,9 .0 11,15 ]heptadecane framework. Honolignols B ( 2 ) and C ( 3 ) were identified as dimers formed via previously unreported C-8′–C-4″ and C-9′–C-4′′ linkages, respectively, connecting two honokiol-derived units. The planar structures and relative configurations of 1 – 3 were established through comprehensive analysis of HRMS (ESI) and 1D/2D NMR data. Chiral HPLC resolution of 1 – 3 afforded three enantiomeric pairs. Their absolute configurations were assigned by experimental and time-dependent density functional theory (TDDFT)-calculated electronic circular dichroism (ECD) spectral comparisons. A proposed biosynthetic pathway of 1 – 3 involving key radical-mediated cascade cyclization steps of honokiol precursors was postulated. The bioactivity evaluation showed that compound (−)- 1 displayed notable antimycoplasma pneumoniae (MP) activity at a concentration of 5 μM; and compounds (+)/(−)- 2 and (+)- 3 exhibited antinonalcoholic steatohepatitis (NASH) activities at a concentration of 20 μM.