2018/05/15 by Daniel H. O’Donovan, Paul Aillard, Martin Berger +6 · 1 citation
Chemistry · Biochemistry, Genetics and Molecular Biology · #Catalytic C–H Functionalization Methods #Synthesis and Catalytic Reactions #Histone Deacetylase Inhibitors Research
paper · pdf · doi:10.1002/anie.201804551
openalex publication_date 2018/05/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.