2002/07/10 by Alec D. Lebsack, J. T. Link, Larry E. Overman +1 · 1 citation
Chemistry · #Synthetic Organic Chemistry Methods #Chemical synthesis and alkaloids #Asymmetric Synthesis and Catalysis
paper · doi:10.1021/ja0267425
openalex publication_date 2002/07/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The first total syntheses of higher-order members of the polypyrrolidinoindoline alkaloid family are reported. The synthesis of quadrigemine C (1) and psycholeine (3) begins with synthetic meso-chimonanthine (4), which is synthesized from commercially available oxindole and isatin in 13 steps and 35% overall yield. Double Stille cross coupling of diiodide 7, available in three steps from 4, with vinylstannane 8 produces dibutenanilide 9. Double catalytic asymmetric Heck cyclization of 9 simultaneously installs the two peripheral quaternary stereocenters and desymmetrizes this advanced meso precursor to deliver the chiral, decacyclic intermediate 11 in 62% yield and 90% ee. In two additional steps, 11 is converted to 1, which upon treatment with acid generates 3. The synthesis of quadrigemine C (1), which rigorously confirms its relative and absolute configuration, was executed in 19 linear steps (2% overall yield) from commercially available starting materials.