Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivatives and Their Neuroprotective Activities.

Twenty natural-product-like 2,8-dioxabicyclo[3.3.1]nonane derivatives were synthesized and their neuroprotective activities were tested using human monoamine oxidases (MAO) A and B and acetyl and butyryl cholinesterases (ChE). Compound 1s showed inhibitory activity for MAO-A, MAO-B and acetylcholinesterase (AChE) (IC50 values 34.0, 2.3 and 11.0 µM, respectively). The inhibition mode of (-)-1s for MAO-B was investigated. Chiral HPLC of (±)-1s separated the enantiomers and (-)-1s showed MAO-B inhibitory activity. Molecular docking simulation of (-)-1s and MAO-B revealed the binding mode.