Synthesis and in vitro antimalarial activity of spiro-analogues of peroxyplakoric acids

Four 1,2,7-trioxa-spiro[5.5]undecanes and two 1,6,7-trioxa-spiro[4.5]decanes were synthesized using the hydrogen peroxide in UHP (urea–H2O2 complex) as the source of the peroxy bond. Incorporation of H2O2 into the organic molecular framework was facilitated by the potential to form a five- or six memberd cyclic hemiketal. Saturation of the double bond in a substituted γ-keto-butenal, a step required in all the syntheses, was achieved in one case with NaI/concd HCl at low temperature without cleaving the TBS protecting group or causing excessive side reactions as observed at ambient temperature. All these peroxides showed in vitro antimalarial activity comparable to that of natural peroxyplakoric acids and the known analogues.