Asymmetric Total Synthesis of (−)-Psychotriadine Featuring [3,3]-Rearrangement and Stereo-Controllable Ring-Contraction
The first asymmetric total syntheses of (-)-psychotriadine (<b>1</b>) and its putative congener tetrahydropsychotriadine (<b>2</b>) were accomplished in 12 and 13 steps, respectively, featuring Meerwein-Eschenmoser-Claisen rearrangement and Fischer indolization/Plancher rearrangement cascade. A stereochemically controllable dearomative ring contraction was utilized to create the vicinal quaternary stereocenters. The absolute configuration was confirmed through X-ray crystallography and >200 mg of <b>1</b> (90% enantiomeric excess (ee)) was obtained. Biological studies revealed that natural product precursor <b>S-10</b> acts as an agonist toward liver X receptors (LXRs, <i>K</i><sub>D</sub> = 1.22/0.79 μM), which upregulates protein levels of ABCA1 and APOE, exhibiting potential as a drug lead in developing medicine for Alzheimer's disease.
Authors
- Tao Xu (ORCID: https://orcid.org/0000-0001-5868-4407)
- Qingxing Yang
- F. Li
- Huizi Ouyang (ORCID: https://orcid.org/0000-0001-7742-124X)
- Haiyong Yu
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Qingdao University of Science and Technology (CN)
- Qingdao Institute of Marine Geology (CN)
- Jimo District Qingdao Hospital of Traditional Chinese Medicine (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1021/jacs.5c11779
- Citations
- 5
- Primary Topic
- Alkaloids: synthesis and pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 7.79
Funders
- National Natural Science Foundation of China
- Qingdao National Laboratory for Marine Science and Technology
- Fundamental Research Funds for the Central Universities