NOVEL REARRANGEMENTS OF THE TRIOXANE RING-SYSTEM OF THE ANTIMALARIAL ARTEETHER UPON TREATMENT WITH ACID IN AN AQUEOUS-METHANOL SOLVENT SYSTEM

While arteether does not have a uv-chromophore, the treatment of artee ther with a HCl, water, methanol system has been previously proposed a s a method of generating a uv-chromophore upon which to base a quantit ative analysis. The present study demonstrates that the originally pro posed structure for the product was not correct and that the reaction is far more complex than originally proposed. It was found that the re action yields 5 different alpha,beta-unsaturated ketones (A-1, A-2, A- 3, A-4, and A-5; whoses strucutres are reported here for the first tim e) that have strong uv chromophores and 4 additional products (new com pounds, B-1 and B-2; previously reported alpha-artemether and beta-art emether) that do not have any significant chromophores. The structure and stereochemistry of these novel reaction products were determined u sing thermospray hplc/ms, H-1-nmr, C-13-nmr, and two-dimensional nmr m ethods.