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C-H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity.

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.

SUBMITTER: O' Donovan DH

PROVIDER: S-EPMC6146912 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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C-H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity.

O' Donovan Daniel H DH Aillard Paul P Berger Martin M de la Torre Aurélien A Petkova Desislava D Knittl-Frank Christian C Geerdink Danny D Kaiser Marcel M Maulide Nuno N

Angewandte Chemie (International ed. in English) 20180622 33

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 ...[more]

PMID: 29761878

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