Neurodegenerative diseases such as Alzheimer’s disease (AD) are a debilitating issue and a social burden. Proactive constituents from herbal ingredients isolated from plants have a crucial role in enhancing memory and neuroprotection in dementia-related disorders. An alkaloid-protopine isolated mostly from the Papaveraceae family exhibited several inhibitory activities against cholinesterase enzyme, which stabilizes the cognitive function of the brain. Several methods for synthesizing protopine are reported the easiest of which is the singlet oxygen oxygenation and ring enlargement of indeno[2, 1-a][3]benzazepines. Crystal and x-ray studies reveal that strong electrostatic interaction between nitrogen atoms in the 10-membered rings stabilizes the protopine structure. Herbs containing protopine are used in folklore medicine in many countries and possess acetylcholinesterase inhibitory (anti-AD), hepatoprotective, and anticancer activity. © 2021 Elsevier Inc. All rights reserved.