Dottorato in SCIENZE FARMACEUTICHE

Titolo della tesi: Enantioselective chromatography based on polysaccharidic stationary phases and synthesis of 10-membered chiral lactones

Abstracts PART A The whole of the results faced and reported in this part deal with the application of polysaccharide-based stationary phases for chiral resolutions of molecules endowed with analytical, synthetic, and pharmaceutical interest. In recent years, the improvements in the field of chiral HPLC and in the design of new enantioselective stationary phases have made liquid chromatography one of the most important separation techniques, currently largely employed in chemical, pharmaceutical and biotechnological industries. In this section, compounds holding chirality either for the presence of stereogenic centres or of asymmetric axis have been studied and methods for their enantioseparations have been developed. The conventional approach for chromatographic separations started by screening several amylose-based and cellulose-based stationary phases as well as the effects of mobile phases and temperature on chiral recognition. Due to the structural complexity of the chiral stationary phase employed, studies that can help to formulate hypotheses of the sites of CSPs involved in the enantioricognition process have been carried out. Moreover, for high throughput discovery of chiral chemicals, HPLC in semi-preparative scale has been performed to collect pure compounds to submit to spectroscopic analysis such as circular dichroism (CD) and optical rotatory dispersion (ORD). PART B This unit reports the results from the period of the academic program at the Complutense University (UCM) of Madrid (ES) in the research group of Prof. Dr. José Carlos Menéndez Ramos, under the supervision of Prof. Dr. Giorgi Giorgio. The goal reached in this study was the development of a non- macrolactonization-based efficient pathway to synthesise lactones of medium-size. During the past decades many cyclization methodologies and ring expansion strategies have been investigated and applied to the preparation of the rare 8- 9- 10- membered lactone, but several difficulties related to enthalpic and entropic stabilization have been encountered. In this work, a reaction scheme based on a medium sized bicyclic-system opening reaction was developed and a small library of 10-membered lactones have been synthetized and their structure was proven by one- and two-dimensional nuclear magnetic spectroscopy (1D- 2D- NMR). The combination between one- dimensional spectroscopy 1H and 13C with two- dimensional homonuclear (COSY) and heteronuclear experiments (HMQC, HMBC) represented an essential tool to provide useful information about the chemical structure, permitting to detect all the structural elements of the achieved compounds. Since the final compounds are chiral, among the future perspectives it is conceivable to design an enantioseparation method for their chiral resolution.