Total Synthesis of (+)-Peganumine A

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.