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C−H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity
We report a novel approach to the classical natural product quinine that is based on two stereoselective key steps, namely a C−H activation and an aldol reaction, to unite the two heterocyclic moieties of the target molecule. This straightforward and flexible strategy enables a concise synthesis of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146912/ https://www.ncbi.nlm.nih.gov/pubmed/29761878 http://dx.doi.org/10.1002/anie.201804551 |
Sumario: | We report a novel approach to the classical natural product quinine that is based on two stereoselective key steps, namely a C−H activation and an aldol reaction, to unite the two heterocyclic moieties of the target molecule. This straightforward and flexible strategy enables a concise synthesis of natural (−)‐quinine, the first synthesis of unnatural (+)‐quinine, and also provides access to unprecedented C3‐aryl analogues, which were prepared in only six steps. We additionally demonstrate that these structural analogues exhibit improved antimalarial activity compared with (−)‐quinine both in vitro and in mice infected with Plasmodium berghei. |
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