郑州大学梅光建/贾世琨JACS:仿生催化实现N-磺酰基联芳内酰胺的阻转异构选择性开环氨解反应

图1. TOC (图片来源于JACS)

摘要：

Amide functional groups are common structural motifs found in many pharmaceuticals and natural compounds. Because of the resonance stability of the amide bond, catalytic enantioselective cleavage of amide C−N bonds still presents stubborn challenges and remains largely unexplored. In nature, metallo-β-lactamases (mβls) cause bacterial resistance toward β-lactam antibiotics via bizinc-catalyzed hydrolytic ring opening of the four-membered β-lactam ring. Inspired by the structures and functions of bizinc mβls, we present here a biomimetic atroposelective ring-opening aminolysis of biaryl lactams via enantioselective cleavage of amide C−N bonds with functional mimics of bizinc mβls, affording two structurally diverse sets of axially chiral biaryl amino amides in high yield with excellent enantioselectivity.

研究背景：

图2. 研究背景及本策略 (图片来源于JACS)

研究内容：

图3. 条件优化 (图片来源于JACS)

图4. 芳胺和联芳内酰胺底物范围 (图片来源于JACS)

图5. 复杂苯胺底物范围 (图片来源于JACS)

图6. 芳胺和N-芳基吲哚内酰胺底物范围 (图片来源于JACS)

图7. 合成应用 (图片来源于JACS)

图8. 其他亲核试剂、非线性效应研究及可能的反应机理 (图片来源于JACS)

图9. DFT计算 (图片来源于JACS)

图10. 过渡态中的弱相互作用 (图片来源于JACS)

总结：

In summary, we have applied the dinuclear zinc catalyst as the reminiscent of the active site of bizinc mβls, materializing biomimetic atroposelective ring-opening aminolysis of biaryl lactams via enantioselective cleavage of amide C−N bonds. With this protocol, two structurally diverse sets of axially chiral biaryl amino amides were furnished in high levels of stereocontrol under mild conditions with non-C₂ symmetric ProPhenol ligands. DFT calculations were performed to understand the mechanism of this transformation, and further explorations of biomimetic synthesis based on dizinc enzymes are ongoing in our laboratory.

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