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

Romanini, Simone (2014) Beyond simple proton transfer processes: domino reactions between 4-substituted indoles and nitroethene as a new gateway to ergot alkaloids. [Laurea magistrale], Università di Bologna, Corso di Studio in Chimica industriale [LM-DM270]
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Abstract

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.

Abstract
Tipologia del documento
Tesi di laurea (Laurea magistrale)
Autore della tesi
Romanini, Simone
Relatore della tesi
Scuola
Corso di studio
Parole chiave
alcaloidi dell'ergot reazioni a cascata reazioni domino catalisi asimmetrica organocatalisi acidi di Broensted indolo nitroetene Friedel-Crafts nitro-Michael
Data di discussione della Tesi
25 Luglio 2014
URI

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