An efficient one-step synthesis of the protoberberine alkaloids karachine, valachine, and sinometumine E is described. This transformation relies on the biosynthetic hypothesis featuring vinylogous aldol, Michael, and Mannich addition reactions working in tandem under mild non-enzymatic conditions. The method employs renewable substrates in an atom-economical and operationally simple manner, allowing for a multigram-scale synthesis. The structure of karachine was confirmed crystallographically and showed the intramolecular n→π* interaction that enabled stereoselective nucleophilic addition to the carbonyl group.

Department of Organic Chemistry Faculty of Science Charles University Hlavova 8 128 00 Praha 2 Czech Republic

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