Synthetic studies toward 1,2-dioxanes as precursors of potential endoperoxide-containing antimalarials

Introduction in therapy of the naturally occurring trioxane artemisinin opened a new era in malaria treatment and prompted the development of semisynthetic and synthetic derivatives characterized by the presence of the key peroxide bridge. The 1,2-dioxane ring is present in some natural endoperoxides such as plakortin and dihydroplakortin, which are endowed with interesting antimalarial properties. Here we describe the development of a versatile stereocontrolled synthetic strategy to 1,2-dioxanes functionalized at the critical C3, C4, and C6 positions, potentially useful for the development of innovative antimalarials.