A general synthetic strategy for antirhine alkaloids was developed in this study. The cyanide-catalyzed imino-Stetter reaction of ethyl 2-aminocinnamate and 4-bromopyridine-2-carboxaldehyde afforded the corresponding indole-3-acetic acid derivative. Subsequent formation of the six-membered C ring followed by trans-selective installation of the two-carbon unit at C-15 provided rapid access to the key intermediate. Stereoselective installation of substituents at C-20 allowed the total syntheses of (±)-antirhine, (±)-18,19-dihydroantirhine, and their 20-epimers, all of the known natural products in the antirhine family.
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government (NRF-2018R1D1A1A02086110 and NRF-2014-011165 Center for New Directions in Organic Synthesis).
© 2020 American Chemical Society.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry