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

Three pairs of racemic honokiol-derived dimeric neolignans, named honolignols A-C (<b>1</b>-<b>3</b>), featuring unique carbon skeletons, were isolated from the barks of <i>Magnolia officinalis</i> var. <i>biloba</i>. Honolignol A (<b>1</b>) 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 (<b>2</b>) and C (<b>3</b>) 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 <b>1</b>-<b>3</b> were established through comprehensive analysis of HRMS (ESI) and 1D/2D NMR data. Chiral HPLC resolution of <b>1</b>-<b>3</b> 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 <b>1</b>-<b>3</b> involving key radical-mediated cascade cyclization steps of honokiol precursors was postulated. The bioactivity evaluation showed that compound (-)-<b>1</b> displayed notable antimycoplasma pneumoniae (MP) activity at a concentration of 5 μM; and compounds (+)/(-)-<b>2</b> and (+)-<b>3</b> exhibited antinonalcoholic steatohepatitis (NASH) activities at a concentration of 20 μM.