2025/04/21 by Bao-Kuan Guo, Yudong Zhang, Ju‐Song Yang +4 · 1 voice · 4 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Alkaloids: synthesis and pharmacology #Asymmetric Synthesis and Catalysis #Asymmetric Hydrogenation and Catalysis
paper · doi:10.1002/anie.202506065
openalex publication_date 2025/04/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/27
The all-carbon quaternary stereogenic center of oxindoles is a crucial structural element of a broad spectrum of indole alkaloids, imparting these molecules with rigid three-dimensional configurations essential for their biological activities. Here, we present a catalytic asymmetric α-ethynylation reaction of oxindoles taking advantage of the catalysis of a spiropyrrolidine amide (SPA) triazolium. This transformation enables the enantioselective construction of the C3 quaternary carbon stereocenter of oxindoles while introducing a versatile ethynyl functionality. Employment of this methodology has been demonstrated in the divergent total synthesis of indole alkaloids (-)-corynoxine, (-)-isorhynchophylline, (-)-aspidospermidine, and (-)-limaspermidine, featuring a protecting group-dependent 1,6-Michael addition or an aminolysis/1,6-Michael addition sequence to generate two distinct types of spiro-indoles, tailored for different late-stage synthetic purposes.