Chiral resolution and bioactivity of enantiomeric furofuran lignans from Juglans mandshurica Maxim

Abstract

Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from Juglans mandshurica Maxim. Subsequently, sesamin was resolved by chiral HPLC to afford a pair of enantiomers, (+)-sesamin (a) and (−)-sesamin (b), in a ratio of approximately 1:3. Their absolute configurations were determined by computational analysis of their electronic circular dichroism (ECD) spectrum. In addition, the pair of enantiomers were evaluated for the inhibition of self-induced Aβ aggregation. Interestingly, (+)-sesamin (a) (67.7%) and (−)-sesamin (b) (80.6%) exhibited different degrees of anti-Aβ aggregation activity. The different inhibition profiles were further explained by molecular dynamics and docking simulation study.