Synfacts 2019; 15(06): 0581
DOI: 10.1055/s-0037-1611621
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Total Synthesis of (–)-Ambiguine

Erick M. Carreira
Moritz Hönig
Xu J, Rawal VH. * The University of Chicago, USA
Total Synthesis of (–)-Ambiguine P.

J. Am. Chem. Soc. 2019;
141: 4820-4823
Further Information

Publication History

Publication Date:
20 May 2019 (online)



Isolated from the cultured cyanobacterium Fischerella ambigua in 2010, ambiguine P belongs to the hapalindole alkaloid family. The pentacyclic natural product contains a seven-membered ring and an embedded indole, which pose significant synthetic challenges. The authors report an enantioselective total synthesis of the target employing a stepwise [4+3]-cycloaddition strategy.



Ketone B, accessible from limonene (A), was transformed into enol ether D in four steps. A net [4+3] cycloaddition of this diene with indole E and subsequent intramolecular Friedel–Crafts reaction installed the target’s pentacyclic core. Functional group manipulations furnished diene I, which was transformed into the natural product by NBS-mediated regioselective oxidation.