Molecules containing endoperoxides such as artemisinin are currently the frontline treatment for malaria. Malaria parasites are showing resistance to current drugs and the development of new therapeutics is of utmost importance. Endoperoxide containing 1,2,4- dioxazinanes are a relatively unknown class of heterocycles and they have potential antimalarial activity. Using a catalyst free, one-pot cascade reaction, novel 1,2,4-dioxazinanes were synthesized from peroxyquinols, aldehydes and alkyl amines. The products were formed in high yields and in high diastereoselectivty via a desymmetrization. A wide range of aldehydes are tolerated in the reaction including aryl, heteroaryl, alkyl, and vinyl. The reaction mechanism is proposed to proceed through imine generation, followed by peroxyhemiaminal formation and aza-Michael reaction.

Diastereoselective one-pot synthesis of endoperoxide containing 1,2,4-dioxazinanes

251st National Meeting (2016)

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