Synthesis of Novel 2-Alkoxy-3-amino-3-arylpropan-1-ols and 5-Alkoxy-4-aryl-1,3-oxazinanes with Antimalarial Activity

A variety of novel <i>syn</i>-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH<sub>4</sub>-promoted reductive ring-opening of <i>cis</i>-3-alkoxy-4-aryl-β-lactams in Et<sub>2</sub>O. The latter γ-aminoalcohols were easily converted into <i>cis</i>-5-alkoxy-4-aryl-1,3-oxazinanes using formaldehyde in THF. Both series of compounds were evaluated against a chloroquine sensitive strain of <i>Plasmodium falciparum</i> (D10), revealing micromolar potency for almost all representatives. Eleven compounds exhibited antimalarial activity with IC<sub>50</sub> values of ≤30 μM, and the majority of these compounds did not show cytotoxicity at the concentrations tested.