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

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journal contribution
posted on 09.07.2009, 00:00 by Matthias D’hooghe, Stijn Dekeukeleire, Karen Mollet, Carmen Lategan, Peter J. Smith, Kelly Chibale, Norbert De Kimpe
A variety of novel syn-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH4-promoted reductive ring-opening of cis-3-alkoxy-4-aryl-β-lactams in Et2O. The latter γ-aminoalcohols were easily converted into cis-5-alkoxy-4-aryl-1,3-oxazinanes using formaldehyde in THF. Both series of compounds were evaluated against a chloroquine sensitive strain of Plasmodium falciparum (D10), revealing micromolar potency for almost all representatives. Eleven compounds exhibited antimalarial activity with IC50 values of ≤30 μM, and the majority of these compounds did not show cytotoxicity at the concentrations tested.