Regioselective Synthesis of Furocoumarin Derivatives and Their Docking and ADME Studies for Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, including dementia, dysphasia, and visual impairments. In this study, substituted hydroxycoumarins 1 were synthesized from ethyl acetoacetate and resorcinol derivatives. The allylation of compounds 1 with allyl bromide involved the hydroxy group to give allyloxycoumarins 2 which underwent regioselective Claisen rearrangement to afford 8-allyl-7-hydroxycoumarins rather than 6-allyl-7-hydroxy-substituted analogues. The subsequent cyclization under various reaction conditions predominantly produced angular furocoumarins (angelicins) over linear isomers (psoralens). A molecular docking study was conducted to evaluate the potential of the synthesized derivatives as anti-Alzheimer agents, and selected compounds were assessed for their drug-likeness properties. The results demonstrated promising activity in comparison to reference drugs.