Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2-Hydroxyphenylbenzimidazole-Based Scaffolds en Route to Donepezil-Like Compounds

Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2-Hydroxyphenylbenzimidazole-Based Scaffolds en Route to Donepezil-Like Compounds

Luca Piemontese, Roberta Sergio, Federica Rinaldo, Leonardo Brunetti, Filippo M. Perna, M. Amélia Santos, Vito Capriati

An unsubstituted 2-hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi-target ligand in Alzheimer’s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so-called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio-renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2-hydroxyphenylbenzimidazole-based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure-activity relationships (SARs).

2020

deep eutectic solvents, 2-hydroxyphenylbenzimidazole, Alzheimer’s disease

DOI: 10.3390/molecules25030574

Molecules

MDPI AG

Organic chemistry

EN