Malaria is an infectious disease caused by protozoan parasites of the genus plasmodium that are transmitted by the female Anopheles mosquito. Chloroquine is perhaps the most commonly known antimalarial belonging to the 4-aminoquinoline class of antimalarials. The emergence of a chloroquine-resistant parasite has made its use obsolete. Amodiaquine and tebuquine (also 4-aminoquinolines) are active against chloroquine-resistant strains of malaria. However, their use has been limited due to harmful side effects resulting from the in vivo oxidation of the aminophenol functionality which is a structural alert for hepatotoxicity as it forms highly reactive and toxic quinone imines (Scheme1a). Replacement of the OH by a similar group that cannot be oxidized is thus desirable. We hypothesize that substitution of OH by CF2H should eliminate in vivo oxidation to toxic metabolites thereby eliminating the dangerous side-effects (Scheme 1b). Herein, we propose a seven step synthetic route for the new series of CF2H analogs and the progress we have made thus far. Once these analogs are synthesized they will be assayed for anti-malarial activity.

Progress toward the synthesis of fluorinated antimalarial analogs

249th National Meeting (2015)

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