NATURE AND GREEN CHEMISTRY AS KEY FACTORS FOR THE SYNTHESIS OF HIGH-QUALITY APIS FOR THE PHARMACEUTICAL INDUSTRY

Climate change has increased the need of an innovative approach to the application of chemistry in all fields with the aim to reduce the environmental impact of pharmaceutical industrial processes. From this perspective, green syntheses are more convenient for pharmaceutical companies and global society due to economic, environmental and safety reasons. Moreover, climate impact of pharmaceutical processes can be reduced by a clever exploitation of nature. Indeed, biomasses are an important source of active pharmaceutical ingredients (APIs) and complex scaffolds that can be used as starting materials or intermediates for the preparations of drugs, reducing hugely the number of synthetic steps. Obviously, a shorter synthesis of an API leads to a decrease of its price, becoming affordable to a larger number of people. In addition to small molecules, peptides are an important class of APIs, and their use has strongly increased during the years. The main drawback of peptides composed by coded amino acids is their poor pharmacokinetic profile due to their proteolytic susceptibility. A trick to improve this property is to insert a non-coded amino acid in the sequence. Taking inspiration from Nature, many researchers investigated the synthesis of new and exotic non-coded amino acids for different purposes and applications both as small molecules or when inserted in peptidomimetics. Nature and Green chemistry were the key factors of my PhD research, which aimed to develop more convenient syntheses of APIs. In particular, the goals of my research are divided into two main topics, involving: 1. the synthesis or semi-synthesis of molecules from Nature inspiration, following the guidelines of Indena S.p.A., the partner who co-funded my PhD grant, together with PON REACT-EU financing Program; 2. the synthesis of non-coded amino acids, coherently with the research field characterizing the research group of the University of Milan, in which I worked in these three years.