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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Asymmetric Total Synthesis of (-)-Psychotriadine Featuring [3,3]-Rearrangement and Stereo-Controllable
Qingxing Yang1, Hanyi Ouyang1, Haiyong Yu1
1Molecular Synthesis Center & Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Abstract:
The first asymmetric total syntheses of (-)-psychotriadine (1) and its putative congener tetrahydropsychotriadine (2) 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 1 (90% enantiomeric excess (ee)) was obtained. Biological studies revealed that natural product precursor S-10 acts as an agonist toward liver X receptors (LXRs, KD = 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.
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