2009/01/01 by Rémi Andres, Qian Wang, Jieping Zhu +1 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Pharmacology, Toxicology and Pharmaceutics · #Alkaloids: synthesis and pharmacology #Catalytic C–H Functionalization Methods #Chemical synthesis and alkaloids #Synthesis and bioactivity of alkaloids #Traditional and Medicinal Uses of Annonaceae
paper · doi:10.1021/jacs.0c05804
openalex publication_date 2009/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01
A five-step total synthesis of arborisidine, a caged pentacyclic monoterpene indole alkaloid, has been accomplished in both racemic and enantioselective manners. The synthesis features the following three key steps: (a) a regioselective Pictet-Spengler reaction of tryptamine with 2,3-pentanedione; (b) a chemo- and stereoselective intramolecular oxidative cyclization; and (c) a complexity-generating aza-Cope/Mannich cascade followed by in situ oxidation and epimerization. A chiral pyrenylpyrrolidino-squaramide catalyzed enantioselective Pictet-Spengler reaction between tryptamine and 2,3-pentanedione is subsequently uncovered, allowing us to develop a five-step asymmetric synthesis of (-)-arborisidine, an enantiomer of the natural substance. Both (±)-19-<i>epi</i>-arborisidine and (-)-19-<i>epi</i>-arborisidine are also synthesized, which undergo epimerization at room temperature in the presence of aqueous 2 N KOH to (±)-arborisidine and (-)-arborisidine, respectively. The 19-<i>epi</i>-isomer is also partially epimerized to arborisidine upon preparative TLC purification (eluent: MeOH/CHCl<sub>3</sub> saturated with NH<sub>3</sub>) and equilibrium studies indicate that arborisidine is thermodynamically more stable than its 19-epimer. In line with Kam's biosynthesis proposal and their purification protocol, we suspect that 19-<i>epi</i>-arborisidine could also be a natural product.