Bioactive Marine Natural Products: Isolation, Structure Elucidation and Synthesis

Marine sponges are a rich source of bioactive compounds which play an important role as protection against predators, overgrowing space competitors, invading microorganisms, and others. Over the past three decades, several biologically active secondary metabolites have been isolated from marine sponges and used to design and develop new therapeutic agents. The work described in this thesis addresses this research topic: the aim is to identify new chemical structures from marine organisms to be used as leads or scaffolds for the elaboration of new drugs. In particular, this PhD thesis consists of two main research activities: - Isolation and structural determination of new bioactive metabolites from marine sponges (Tedania ignis, Pseudaxinella flava and Plakortis simplex); - Synthesis of an analogue of simplexide, a glycolipid with an important immunoregulatory role. The results obtained from the chemical and pharmacological characterization of the new bioactive metabolites from marine sponges are here summarized: 1.00 2.00 3.00 The second line of research concerns a project focused on the synthesis of an analogue of simplexide, a glycolipid isolated from the Caribbean sponge Plakortis simplex in the year 1999. The simplexide showed to be a potent stimulus for the production of cytokines and chemokines, with interesting perspectives to be used in cancer and autoimmune diseases. In order to better understand the mechanism of action on immune system, the synthesis of a simpler analogue, having only a sugar in the saccharide chain, was carried out. Several synthetic approaches were applied, focusing on β-glycosilation step. The reactions were performed using conventional and microwave heating. Although the yields need further optimizations, the amount of the analogue of simplexide obtained so far will be tested on human blood monocytes.