A Sustainable Synthetic Approach to Tacrine and Cholinesterase Inhibitors in Deep Eutectic Solvents under Aerobic Conditions
Luciana Cicco,
Filippo Maria Perna,
Vito Capriati,
Paola Vitale
Affiliations
Luciana Cicco
Dipartimento di Farmacia—Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Consorzio Interuniversitario Nazionale “Metodologie e Processi Innovativi di Sintesi” (C.I.N.M.P.I.S.), Via E. Orabona 4, I-70125 Bari, Italy
Filippo Maria Perna
Dipartimento di Farmacia—Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Consorzio Interuniversitario Nazionale “Metodologie e Processi Innovativi di Sintesi” (C.I.N.M.P.I.S.), Via E. Orabona 4, I-70125 Bari, Italy
Vito Capriati
Dipartimento di Farmacia—Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Consorzio Interuniversitario Nazionale “Metodologie e Processi Innovativi di Sintesi” (C.I.N.M.P.I.S.), Via E. Orabona 4, I-70125 Bari, Italy
Paola Vitale
Dipartimento di Farmacia—Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Consorzio Interuniversitario Nazionale “Metodologie e Processi Innovativi di Sintesi” (C.I.N.M.P.I.S.), Via E. Orabona 4, I-70125 Bari, Italy
An enhanced, sustainable, and efficient method for synthesizing tacrine, achieving a 98% yield, has been developed by replacing volatile organic compounds with more eco-friendly solvents such as deep eutectic solvent (DESs). The optimized protocol scales easily to 3 g of substrate without yield loss and extends successfully to tacrine derivatives with reduced hepatotoxicity. Particularly notable is the synthesis of novel triazole-based derivatives, yielding 90–95%, by integrating an in situ preparation of aryl azides in DESs with N-propargyl-substituted tacrine derivatives. Quantitative metrics validate the green aspects of the reported drug development processes.
