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New Experimental Conditions for Diels-Alder and Friedel-Crafts Alquilation Reactions with Thiophene: A New Selenocyanate with Potent Activity against Cancer.

Gorka Calvo-MartínDaniel PlanoCarmen Sanmartin
Published in: Molecules (Basel, Switzerland) (2022)
The reactivity of thiophene in Diels-Alder reactions is investigated with different maleimide derivatives. In this paper, we have synthesized for the first time the Diels-Alder adducts of thiophene at room temperature and atmospheric pressure. Maleimido-thiophene adducts were promoted by AlCl 3 . The effects of solvent, time, temperature and the use of different Lewis acids were studied, showing dramatic effects for solvent and Lewis acid. Furthermore, the catalysis with AlCl 3 is highly stereoselective, preferably providing the exo form of the adduct. Additionally, we also discovered the ability of AlCl 3 to catalyze the arylation of maleimides to yield 3-aryl succinimides in a straightforward manner following a Friedel-Crafts-type addition. The inclusion of a selenocyanate group contributes to the cytotoxic activity of the adduct. This derivatization (from compound 7 to compound 15 ) results in an average GI 50 value of 1.98 µM in the DTP (NCI-60) cell panel, resulting in being especially active in renal cancer cells.
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