| Autor: |
Wanner, Daniel M., Becker, Patrick M., Suhr, Simon, Wannenmacher, Nick, Ziegler, Slava, Herrmann, Justin, Willig, Felix, Gabler, Julia, Jangid, Khushbu, Schmid, Juliane, Hans, Andreas C., Frey, Wolfgang, Sarkar, Biprajit, Kästner, Johannes, Peters, René |
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| Zdroj: |
Angewandte Chemie International Edition; Sep2023, Vol. 62 Issue 36, p1-12, 12p |
| Abstrakt: |
Pyrazolones represent an important structural motif in active pharmaceutical ingredients. Their asymmetric synthesis is thus widely studied. Still, a generally highly enantio‐ and diastereoselective 1,4‐addition to nitroolefins providing products with adjacent stereocenters is elusive. In this article, a new polyfunctional CuII‐1,2,3‐triazolium‐aryloxide catalyst is presented which enables this reaction type with high stereocontrol. DFT studies revealed that the triazolium stabilizes the transition state by hydrogen bonding between C(5)−H and the nitroolefin and verify a cooperative mode of activation. Moreover, they show that the catalyst adopts a rigid chiral cage/pore structure by intramolecular hydrogen bonding, by which stereocontrol is achieved. Control catalyst systems confirm the crucial role of the triazolium, aryloxide and CuII, requiring a sophisticated structural orchestration for high efficiency. The addition products were used to form pyrazolidinones by chemoselective C=N reduction. These heterocycles are shown to be valuable precursors toward β,γ'‐diaminoamides by chemoselective nitro and N−N bond reductions. Morphological profiling using the Cell painting assay identified biological activities for the pyrazolidinones and suggest modulation of DNA synthesis as a potential mode of action. One product showed biological similarity to Camptothecin, a lead structure for cancer therapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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