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Updated: Jul 15, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Exploring NiCl2, PdCl2 and PtCl2 as a catalyst for [3 + 2] cycloaddition in Kopsane alkaloid synthesis by density
Sanghee Yoon1, Pratanphorn Nakliang1, Bilal Shaker1
1Global AI Drug Discovery Center, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
None:
Kopsane alkaloids possess a complex heptacyclic scaffold and exhibit significant biological activities, including cholinergic, anti-inflammatory, and anti-cancer effects. While we previously reported PtCl2-catalyzed [3 + 2] cycloaddition for their synthesis, the high cost and toxicity of platinum necessitate sustainable alternatives. In this study, we employed density functional theory (DFT) to investigate MCl2 (M = Ni, Pd, and Pt) catalyzed [3 + 2] cycloaddition in Kopsane alkaloid synthesis. Our results indicate consistent reaction characteristics across all metals, with the second cyclization acting as the diastereoselectivity-determining step. The calculated energy gaps between transition states (TS2s) for NiCl2, PdCl2, and PtCl2 were 5.57, 1.45, and 12.25 kcal/mol, respectively. These energy profiles suggest that NiCl2 can achieve high diastereoselectivity similar to PtCl2 due to its significant energy gap (> 4 kcal/mol). The implementation of this computational chemistry technique provides theoretical evidence that could help to improve the efficiency of the catalyst designing process.
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