Xu J,
Rawal VH.
* The University of Chicago, USA
Total Synthesis of (–)-Ambiguine P.
J. Am. Chem. Soc. 2019;
141: 4820-4823
Key words
Friedel–Crafts reaction - [4+3] cycloaddition - ambiguine P - hapalindole alkaloids
Significance
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.
Comment
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.
