Sustainable synthesis of biologically active molecules

Zusammenfassung

The herein exposed dissertation is conceived based on the implementation and use of Green Chemistry. The increased interest in this branch of chemistry has involved not only academia but also companies that are required to be more environmentally sustainable. The urge to reduce the environmental impact of the chemical processes and consequently the pollutions sources related to them has prompted the scientific community to define new greener methodologies for the synthesis of fine chemicals, pharmaceuticals and polymers. In a chemical process, the parameters that have to be carefully optimized from a point of view of sustainability are the chemical efficiency, amount and origin of the solvents, reaction conditions (e.g. temperature and pressure), the need and the number of purification steps, and the over stoichiometric use of reagents and promoters. The present work aims to develop novel synthetic protocols for the synthesis of biologically active molecules able to minimize energy misuse and waste production. This PhD thesis is divided into two chapters connected by the common green approach to the synthesis of molecules of pharmaceutical interest. In Chapter 1, two libraries of antiproliferative drugs were synthesized using a green by design approach. A thorough study of their biological efficacy in cells and their Structure-Activity-Relationships (SARs) have been evaluated. On the other hand, in Chapter 2, well-known drug scaffolds were synthesized using innovative and greener procedures. In particular, the use of Manganese OMS-2 as heterogeneous catalyst in C-H activation and oxidative reactions was exploited. Its reusability and low leaching allowed the integration of such system into a flow apparatus. The multidisciplinary scenario in which this thesis has evolved is mostly thanks to our collaborators. In Chapter 1, the biological assays (enzyme inhibition and cell growth proliferation) were carried out by Prof. María Paz Carrasco Jiménez of the Department of Biochemistry in the Faculty of Sciences at the University of Granada. The fluorescence spectra and the use of FLIM equipment were as well the main work of the PhD. Laura Espinar Barranco, who set up the experiment to be recorded. In Chapter 2, the first part was developed hand in hand with Dr Francesco Ferlin and under the supervision of both Prof. Vaccaro of the Department of Chemistry, Biology and Biotechnology at the University of Perugia and my PhD supervisor Prof. Lanari. However, while I was responsible for the synthesis of starting materials to be tested, Dr Ferlin designed the flow system and set up conditions for its use.