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C-H activation enables a concise total synthesis of quinine and analogues with enhanced antimalarial activity

O' Donovan, Daniel H. and Aillard, Paul and Berger, Martin and de la Torre, Aurélien and Petkova, Desislava and Knittl-Frank, Christian and Geerdink, Danny and Kaiser, Marcel and Maulide, Nuno. (2018) C-H activation enables a concise total synthesis of quinine and analogues with enhanced antimalarial activity. Angewandte Chemie (International ed. in English), 57 (33). pp. 10737-10741.

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Abstract

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1433-7851
e-ISSN:1521-3773
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:12 Oct 2018 14:26
Deposited On:12 Oct 2018 14:24

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