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

Author(s)

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

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 8, n. 36, p. 10-pg., 2023-09-26.

Abstract

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)

• FAPESP's process: 20/12530-8 - 2-(Trimethylsilyl)aryl trifluoromethanesulfonates as aryne precursors aiming to the preparation of functionalized (hetero)aromatic compounds and syntheses of bioactive natural products
• Grantee: Cristiano Raminelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/20796-2 - Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/04709-8 - Evaluation of potential therapeutically compounds for SARS-CoV-2: focus on estrogen-related compounds, autophagy modulators and ACE2
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Regular Research Grants