Piemontesi C, Wang Q, Zhu J * École Polytechnique Fédérale de Lausanne, Switzerland
Enantioselective Synthesis of (+)-Peganumine A.
J. Am. Chem. Soc. 2016;
138: 11148-11151
Key words
(+)-peganumine A - Passerini reaction - Pictet–Spengler reaction - thiourea catalysis
Significance
(+)-Peganumine A, isolated from the seeds of Peganum harmala L., is a dimeric tetrahydro-β-carboline alkaloid displaying significant selective cytotoxic
activity against HL-60 cells (IC50 = 5.8 μM). The first enantioselective synthesis by Zhu and co-workers relies on an
early Liebeskind–Srogl cross-coupling and a thiourea-catalyzed Pictet–Spengler reaction
to form the unprecedented octacyclic scaffold.
Comment
Liebeskind–Srogl cross-coupling of stannane B and thioester C provided N-formamide E in 95% yield. After dehydration, a three-center-two-component Passerini reaction
followed by oxidation furnished tetracycle H. The synthesis was completed by an enantioselective Pictet–Spengler reaction of H and 6-methoxytryptamine (A) to give (+)-peganumine A in a total of 7 steps and 33% overall yield.
