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
Affiliations
Luca Piemontese
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
Roberta Sergio
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
Federica Rinaldo
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
Leonardo Brunetti
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
Filippo M. Perna
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
M. Amélia Santos
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal
Vito Capriati
Dipartimento di Farmacia–Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Via E. Orabona 4, I-70125 Bari, Italy
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).
