• Incretin
• Hetero-Cope rearrangement
• GLP-1
• Diabetes
• 1 3-diaza-4-oxa-[3.3.1]-nonene
• 1 2-dihydropyridines
• Nitroso Diels-Alder
• Super hydride

Diabetes is among the most common and prominent disease in various countries of the world and in particular, type-2 diabetes is prevalent in 90% of the population suffering from diabetes.
Recently an interesting new target for this disease has been identified as the glucagon like peptide receptor (GLP-1R): this protein is activated by Glucagon-like peptide (GLP)-1 and the insulin secretion is enhanced in a glucose dependent manner. In addition, such binding reduces food intake by inhibiting gastric acid secretion and slows down gastric empty, possibly through a central effect, and causes weight loss. Therefore, (GLP)-1 mimicking drugs have been extensively studied and currently some of them have been approved, but they all belongs to peptide-based scaffolds, so the only method of administration is by injection.
In our laboratory we have developed a new synthetic strategy for the obtainment of a novel 1,3-diaza-4-oxa-[3.3.1]-nonene framework. This has been achieved by a series of reactions that provide the elaboration of inverse nitroso cycloadducts derived from 2-substituted-1,2-dihydropyridines, to give 4a,7,8,8a-tetrahydropyrido[4,3-e]-1,4,2-dioxazines through a [3,3]-hetero Cope rearrangement; ultimately, the use of an excess of highly reactive lithium triethylborohydride allowed us to afford the target molecule that has already been proved to be of a GLP-1 agonist in the micromolar range.
In my Thesis work, I focused my attention on the synthesis of a library of 1,3-diaza-4-oxa-[3.3.1]-bicyclic compounds characterized by different aromatic substituents with the goal of rationalize their eventual biological activity with respect to their structure. Interestingly, considering the low molecular weight of these derivatives, they could be even administrated orally.
All the new molecules obtained during our synthetic effort have been thoroughly analysed and characterized through NMR and HPLC-Mass experiments. The biological activity (GLP-1 Secretion mSTC-1 SP / CRC and GLP-1 Secretion Glu-Tag SP / CRC) of the obtained compounds are currently under investigation.