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

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.