Synthesis Of Donepezil Research Articles

Front Cover: Sequential‐Flow Synthesis of Donepezil: A Green and Sustainable Strategy Featuring Heterogeneous Catalysis and Hydrogenation (Chem. Eur. J. 59/2024)

Front Cover: Sequential‐Flow Synthesis of Donepezil: A Green and Sustainable Strategy Featuring Heterogeneous Catalysis and Hydrogenation (Chem. Eur. J. 59/2024)

Molecular Modelling Based Design and Synthesis of Donepezil Like Derivatives As Acetylcholinesterase Inhibitors

Alzheimer's disease (AD) is the most common form of dementia, a general term for memory loss and other cognitive abilities. This disorder is well associated with an impairment in cholinergic transmission. Therefore, cholinesterase inhibition leads to revert of putative deficit in acetylcholine levels in AD and thus might reverse the memory impairment characteristics. A series of compounds were rationally designed by taking donepezil as a lead molecule by using molecular modeling studies. All the designed compounds were analyzed by calculating their dock scores to check their probable binding affinities within the active site of acetylcholinesterase enzyme. Among all the compounds, six compounds showed significant dock score within the active site of enzyme which suggest that these molecules could effectively block the catalytic activity of enzyme. Compounds with nitro groups on the terminal benzyl moiety were found to be most prominent ones and could act as hit lead for the further development of acetylcholinesterase inhibitors. In silico study of all the compounds were also performed by using computational Marvin Sketch software which describes the compliance of all the designed compounds with the Lipinski rule of five. Furthermore, potent compounds were synthesized and characterized by using 1H & 13C NMR and MASS spectroscopic techniques were sent for further biological evaluations.

Nickel-Catalyzed Hydrogen-Borrowing Strategy for α-Alkylation of Ketones with Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones.

The α-alkylation of ketones using an earth-abundant and nonprecious NiBr2/L1 system is reported. This nickel-catalyzed reaction could be performed in gram scale and successfully applied in the synthesis of donepezil (Alzheimer's drug) and functionalization of steroid hormones and fatty acid derivatives. Synthesis of N-heterocycles, methylation of ketones, and one-pot double alkylation to bis-hetero aryl ketones using two different alcohols with a single catalyst broadens the scope of the catalytic protocol. Preliminary mechanistic studies using defined Ni-H species and deuterium-labeling experiments established the participation of the borrowing-hydrogen strategy.

Direct carbocyclizations of benzoic acids: catalyst-controlled synthesis of cyclic ketones and the development of tandem aHH (acyl Heck-Heck) reactions.

The formation of exo-methylene indanones and indenones from simple ortho-allyl benzoic acid derivatives has been developed. Selective formation of the indanone or indenone products in these reactions is controlled by choice of ancillary ligand. This new process has a low environmental footprint as the products are formed in high yields using low catalyst loadings, while the only stoichiometric chemical waste generated from the reactants in the transformation is acetic acid. The conversion of the active cyclization catalyst into the Hermman-Beller palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction, and utilized in the synthesis of donepezil.

Efficient and Industrially Viable Synthesis of Donepezil

An efficient, economically viable process has been developed for large‐scale preparation of donepezil HCl (1), an anti‐Alzheimer's agent. The process involves the condensation of 5,6‐dimethoxy‐1‐indanone (3) and 1‐benzyl‐4‐piperidinecarboxaldehyde (4) in the presence of alkalimetal carbonates at elevated temperature to yield 1‐benzyl‐4‐[(5,6‐dimethoxy‐1‐indanone)‐2‐yidenyl] methyl piperidine (2), the key intermediate in the synthesis of donepezil. Hydrogenation of 2 yields donepezil.

New Synthesis of Donepezil Through Palladium‐Catalyzed Hydrogenation Approach.

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New Synthesis of Donepezil Through Palladium‐Catalyzed Hydrogenation Approach

A new, economical, and efficient process has been developed for large‐scale synthesis of donepezil 1, an anti‐Alzheimer's drug. The process involves palladium‐catalyzed hydrogenation of (2E)‐5,6‐di...