Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid.

The reaction of trioxane and tetraoxane endoperoxides with unsaturated phospholipid 1 in the presence of Fe(II) was investigated in the absence of oxygen by means of tandem ESI-MS analysis. The spectral analyses for the reaction mixtures showed that artemisinin 2 with a trioxane structure gave no peak except that for the remaining intact phospholipid 1 (m/z 758.9), indicating that there was no structural change to 1.

A combination of unnatural phosphatidyl acceptor and tandem electrospray ionization mass spectrometry for tracing phospholipase D activity.

Phospholipase D (PLD) is a biocatalyst in the synthesis of bioactive compounds and a key enzyme in a variety of biological signal transductions. A combination of unnatural phosphatidyl acceptor, N,N,N-triethyl-N-2-hydroxyethylammonium bromide 6, as a substrate for PLD, and tandem electrospray ionization mass spectrometry (ESI MS) was found to provide information as to whether a given phospholipid serves as a substrate for the PLD-catalyzed reaction. Thus 2-(13'-hydroperoxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 1, and its degradation products 2-(13'-oxo-octadecadienoyl)-1-palmitoylglycerophosphocholine 9 and 2-(13'-hydroxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 11, in a mixture were found to be a substrate of the PLD-catalyzed transphosphatidylation.

Synthesis of novel conjugates of tetraoxane endoperoxide with bis(quaternary ammonium salts).

Novel water-soluble conjugates of 1,2,4,5-tetraoxane bis(quaternary ammonium salts) were synthesized in a relatively stable crystalline form via four steps starting from methyltrioxorhenium-catalyzed endo-peroxidation of ethyl 4-oxocyclohexanecarboxylate with hydrogen peroxide in hexafluoro-2-propanol. The assay for the in vitro toxicity of water-soluble tetraoxanes 5a-5d to malaria parasites indicate that they were inactive against the Plasmodium falciparum FCR-3 strain.

Synthesis and biological activity of fatty acid derivatives of quinine.

Derivatives of quinine with fatty acids including polyunsaturated fatty acids were prepared. They showed moderate antimalarial activity as compared with quinine itself using Plasmodium falciparum. The activities were not dependent on whether the fatty acyl group was saturated or unsaturated.