Abstract
A concise asymmetric total synthesis of a group of tetrahydroprotoberberine alkaloids, (-)-canadine, (-)-rotundine, (-)-sinactine, and (-)-xylopinine, has been accomplished in three steps from the commercially available corresponding disubstituted phenylethylamine and disubstituted benzaldehyde. Our synthesis toward these four alkaloids took advantage of the following strategy: in the first step, we achieved an efficient and sustainable synthesis of secondary amine hydrochlorides via a fully continuous flow; in the second step, we developed a Pictet-Spengler reaction/Friedel-Crafts hydroxyalkylation/dehydration cascade for the construction of the dihydroprotoberberine core structure (ABCD-ring); and in the last step, Ir-catalyzed enantioselective hydrogenation was employed for the introduction of the desired stereochemistry at the C-14 position in the tetrahydroprotoberberine alkaloids. This work significantly expedites the asymmetric synthesis of the entire tetrahydroprotoberberine alkaloid family as well as a more diverse set of structurally related non-natural analogues.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
