An Efficient and Industrially Scalable Total Synthesis of Anti-Alzheimer Drug Donepezil

Abstract

Alzheimer's disease, a chronic neurodegenerative disease which usually starts slowly and worsens over time. Alzheimer's disease individuals exhibit retrogression in mental health functions rendering them incapacitated and unable to perform normal daily activities. Elderly persons are the ones commonly afflicted with this disease. However, evidence shows that it can also afflict even individuals as young as 40 years of age. It is a kind of dementia has no cure and in time leads to death. Donepezil is a well-known drug used to treat Alzheimer's disease. Donepezil hydrochloride is the second drug approved by the United States food and drug administration (FDA) for the treatment of mild to moderate alzheimer's diseases (AD). It is a new class of acetyl cholinesterase (AChE) inhibitor having an N-benzylpiperidine and an indanone moiety that shows longer and more selective action. Donepezil HCl, a piperidine derivative, is a highly selective inhibitor of the enzyme AChE that is chemically unique from other AChE inhibitors. In vitro and preclinical studies have demonstrated that Donepezil is much more selective for AChE in the brain than for butyrylcholinesterase (BuChE) in the periphery. Various methods for the synthesis of donepezil and an improved, industrially scalable total synthesis are presented in this chapter. Physical properties and pharmacology are also included.