C−H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity
| Autor: | Daniel H. O' Donovan, Christian Knittl-Frank, Martin Berger, Marcel Kaiser, Nuno Maulide, Danny Geerdink, Desislava Petkova, Aurélien de la Torre, Paul Aillard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Stereochemistry
Plasmodium berghei Molecular Conformation malaria 010402 general chemistry Crystallography X-Ray 01 natural sciences Catalysis Ruthenium C−H activation chemistry.chemical_compound Antimalarials Mice Aldol reaction medicine Animals quinine total synthesis Quinine Aldehydes Natural product biology 010405 organic chemistry Total synthesis Stereoisomerism General Chemistry biology.organism_classification Carbon 0104 chemical sciences 3. Good health chemistry Stereoselectivity medicine.drug Hydrogen |
| Zdroj: | Angewandte Chemie International Edition |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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