Catalytic Enantioselective α‐Ethynylation of Oxindoles: Total Synthesis of (‐)‐Corynoxine, (‐)‐Isorhynchophylline, (‐)‐Aspidospermidine, and (‐)‐Limaspermidine
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.
Authors
- Bao-Kuan Guo
- Xiao‐Ming Zhang (ORCID: https://orcid.org/0000-0002-9294-9672)
- Fu‐Min Zhang (ORCID: https://orcid.org/0000-0001-5578-1148)
- Yong‐Qiang Tu (ORCID: https://orcid.org/0000-0002-9784-4052)
- Yudong Zhang (ORCID: https://orcid.org/0000-0002-7812-2345)
- Jin-Rui Tian
- Ju‐Song Yang (ORCID: https://orcid.org/0009-0006-2432-1505)
Institutions
- Shanghai Jiao Tong University (CN)
- Shanghai Innovative Research Center of Traditional Chinese Medicine (CN)
- Lanzhou University (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-04-21
- DOI
- https://doi.org/10.1002/anie.202506065
- Citations
- 3
- Primary Topic
- Alkaloids: synthesis and pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 4.67