Beyond simple proton transfer processes: domino reactions between 4-substituted indoles and nitroethene as a new gateway to ergot alkaloids

The multimodal biology activity of ergot alkaloids is known by humankind since middle ages. Synthetically modified ergot alkaloids are used for the treatment of various medical conditions. Despite the great progress in organic syntheses, the total synthesis of ergot alkaloids remains a great challenge due to the complexity of their polycyclic structure with multiple stereogenic centres. This project has developed a new domino reaction between indoles bearing a Michael acceptor at the 4 position and nitroethene, leading to potential ergot alkaloid precursors in highly enantioenriched form. The reaction was optimised and applied to a large variety of substrate with good results. Even if unfortunately all attempts to further modify the obtained polycyclic structure failed, it was found a reaction able to produce the diastereoisomer of the polycyclic product in excellent yields. The compounds synthetized were characterized by NMR and ESIMS analysis confirming the structure and their enantiomeric excess was determined by chiral stationary phase HPLC. The mechanism of the reaction was evaluated by DFT calculations, showing the formation of a key bicoordinated nitronate intermediate, and fully accounting for the results observed with all substrates. The relative and absolute configuration of the adducts were determined by a combination of NMR, ECD and computational methods.

Evaluation of Th and U contamination in the CUORE experiment using a delayed coincidence analysis

The discovery of the neutrino mass is a direct evidence of new physics. Several questions arise from this observation, regarding the mechanism originating the neutrino masses and their hierarchy, the violation of lepton number conservation and the generation of the baryon asymmetry. These questions can be addressed by the experimental search for neutrinoless double beta (0\nu\beta\beta) decay, a nuclear decay consisting of two simultaneous beta emissions without the emission of two antineutrinos. 0\nu\beta\beta decay is possible only if neutrinos are identical to antineutrinos, namely if they are Majorana particles. Several experiments are searching for 0\nu\beta\beta decay. Among these, CUORE is employing 130Te embedded in TeO_2 bolometric crystals. It needs to have an accurate understanding of the background contribution in the energy region around the Q-value of 130Te. One of the main contributions is given by particles from the decay chains of contaminating nuclei (232Th, 235-238U) present in the active crystals or in the support structure. This thesis uses the 1 ton yr CUORE data to study these contamination by looking for events belonging to sub-chains of the Th and U decay chains and reconstructing their energy and time difference distributions in a delayed coincidence analysis. These results in combination with studies on the simulated data are then used to evaluate the contaminations. This is the first time this analysis is applied to the CUORE data and this thesis highlights the feasibility of it while providing a starting point for further studies. A part of the obtained results agrees with ones from previous analysis, demonstrating that delayed coincidence searches might improve the understanding of the CUORE experiment background. This kind of delayed coincidence analysis can also be reused in the future once the, CUORE upgrade, CUPID data will be ready to be analyzed, with the aim of improving the sensitivity to the 0\nu\beta\beta decay of 100Mo.