# Synthesis and Antimicrobial Activity of Canthin-6-One Alkaloids

## TL;DR

Scientists synthesized new canthin-6-one alkaloids and tested their antimicrobial effects against several pathogens.

## Contribution

The study reports the first synthesis of four canthin-6-one alkaloids and eight new derivatives, along with their antimicrobial activity against human pathogens.

## Key findings

- Seventeen compounds, including nine canthin-6-ones, were synthesized and structurally confirmed.
- Alkaloids 1-4 and 9 showed antimicrobial activity against C. albicans, C. neoformans, and S. aureus at 50 µg/mL.
- The antimicrobial activity of compounds 2, 4-5, and 12-13 against four human pathogens is reported for the first time.

## Abstract

Canthin-6-one alkaloids have consistently attracted the interest of medicinal chemists due to their wide range of promising bioactivities, including antitumor, antifungal, antibacterial, and antiviral properties. However, their low natural abundance in plants has constrained the further exploration of their potential bioactivities. This study reports a comprehensive synthesis of canthin-6-one alkaloids, utilizing key Suzuki coupling and Cu-catalyzed amidation reactions to construct their core scaffold. Derivatives were synthesized with Koenig–Knorr glycosylation for the further modification of synthetic canthin-6-ones. The antimicrobial activities of the synthesized compounds were evaluated against C. albicans, C. neoformans, S. aureus and E. coli using the micro-dilution method. In total, 17 compounds were synthesized, including nine canthin-6-ones. Notably, alkaloids 4, 5, 7 and 12-13 were prepared for the first time, along with 8 new derivatives. Their structures were confirmed by NMR and MS analyses. At 50 µg/mL, the alkaloids 1-4 and 9 exhibited antimicrobial properties against C. albicans, C. neoformans and S. aureus. The antimicrobial activity of alkaloids 2, 4-5 and 12-13 against these four microbial human pathogens is reported here for the first time. Overall, this research not only advances our understanding of canthin-6-one alkaloid synthesis, but also provides a foundation for developing novel compounds with pharmaceutical properties.