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Beyond Pseudo-natural Products: Sequential Ugi/Pictet-Spengler Reactions Leading to Steroidal Pyrazinoisoquinolines
Fernando Alonso1,2, Agustín Galilea1,2, Pau Arroyo Mañez1,3
1Departamento de Química Orgánica, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, 1428, Argentina.
Abstract:
In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet-Spengler cyclization on steroid-derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase-independent cell-death mechanism, an appealing feature when new antitumor compounds are searched.
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