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