Total Synthesis of Aleutianamine.

Abstract

Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC50 of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic carbonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.

• Authors: Hao Yu, Zachary P Sercel, Samir P Rezgui, Jonathan Farhi, Scott C Virgil, Brian M Stoltz
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 145 Issue 47 Pg. 25533-25537 (Nov 29 2023) ISSN: 1520-5126 [Electronic] United States
• PMID: 37967164 (Publication Type: Journal Article)

Chemical References

• Palladium
• Biological Products

Topics

• Humans
• Palladium
• Catalysis
• Stereoisomerism
• Amination
• Biological Products