Total Synthesis of Aporphine Alkaloids via Benzyne Chemistry: Progress Towards a Late-Stage Enantioselective Hydrogenation and Neuroprotective Activity Evaluations

Autor(es)

Cipriano da Silva, Tamiris Reissa ; Oliveira, Rafaela Brito ; Nicastro, Arthur Luiz Miranda ; Ureshino, Rodrigo Portes ; Raminelli, Cristiano

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRYSELECT; v. 8, n. 36, p. 10-pg., 2023-09-26.

Resumo

A dehydroaporphine intermediate obtained via benzyne chemistry was used to accomplish the enantioselective total synthesis of (S)-nuciferine, the first total synthesis of (& PLUSMN;)-urabaine, and our second-generation total synthesis of lysicamine. (S)-Nuciferine was obtained by an unprecedented late-stage asymmetric hydrogenation employing a chiral iridium(I) catalyst. The first total synthesis of (& PLUSMN;)-urabaine and the second-generation total synthesis of lysicamine, which exhibited low cytotoxicity and neuroprotective activity, were completed by oxidation reactions in 7 and 6 steps, respectively. The enantioselective total synthesis of (S)-nuciferine, the first total synthesis of (& PLUSMN;)-urabaine, and our second-generation total synthesis of lysicamine were accomplished employing a dehydroaporphine intermediate obtained via benzyne chemistry, an unprecedented late-stage asymmetric hydrogenation, and oxidation reactions. Lysicamine and (& PLUSMN;)-urabaine presented low cytotoxicity and promising neuroprotective activity.image (AU)

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