Nickel Catalyst Builds Mirror-Image Drug Scaffolds
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- Prof. Sangwon Seo's team at DGIST developed a nickel catalytic system that synthesizes β-methylene carbonyl derivatives — a core scaffold in many pharmaceuticals — exclusively in one mirror-image isomer form
- The nickel-based approach directly couples alkynes and carbonyl compounds, achieving near-perfect regioselectivity and enantioselectivity while avoiding the strong bases or complex auxiliary groups previously required
- Nickel was chosen over expensive noble metals as an earth-abundant, inexpensive transition metal, addressing a long-standing challenge in stereoselective synthesis
- The reaction proceeds reliably in complex molecular structures and tolerates diverse functional groups, with the team successfully modifying complex pharmaceutical structures and constructing natural-product scaffolds at a level 'suitable for commercialization'
- Density functional theory (DFT) computational analysis was used to elucidate the mechanism by which the nickel catalyst controls bond formation and three-dimensional structure
- The research, published in Angewandte Chemie International Edition, is positioned as relevant to precision chemistry and new drug development where one mirror-image form may be therapeutic while its counterpart is inactive or toxic
Why it matters: Pharmaceutical manufacturers typically rely on expensive noble-metal catalysts to produce enantiopure drugs, where the wrong mirror-image isomer can be inactive or toxic. This nickel-based alternative uses an earth-abundant metal and simpler feedstocks (alkynes and carbonyls), potentially lowering production costs for β-methylene carbonyl scaffolds found in numerous drug candidates — and the team demonstrated the method works on complex pharmaceutical structures at a 'level suitable for commercialization.'
