anhydrodihydroartemisinin and deoxyartemisinin

Photooxygenation of anhydrodeoxydihydroartemisinin (4) followed by chromatographic separation of the reaction mixture yielded the new compounds alpha- (5) and beta-hydroperoxydeoxyartemisitene (8) and the formate ester 7, together with two previously reported compounds, 6 and 9. Reduction of 5 using polymer-bound triphenylphosphine afforded the new compound dihydrodeoxyartemisitene (10). Treatment of 10 with a catalytic amount of BF(3)-OEt(2) yielded the C(2)-symmetrical dimer bis(dihydrodeoxyartemisitene) ether (11) and two new compounds, dihydrodeoxyartemisitene methyl ether (12) and the dimer 13, as minor products. Dehydroacetoxylation of 5 using acetic anhydride in pyridine afforded deoxyartemisitene (14). The identities of the new compounds (5, 7, 8, 10-14) were deduced from their spectral data and by chemical derivatization. The stereochemistry of dimer 11 was defined on the basis of X-ray crystallographic analysis. All compounds were evaluated in vitro in the National Cancer Institute drug-screening program consisting of 60 human cancer cell lines derived from nine different tissues. Of the compounds tested, deoxyartemisitene (14) demonstrated significant cytotoxicity against a number of human cancer cell lines.

Topics: Antineoplastic Agents, Phytogenic; Artemisia; Artemisinins; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Female; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Oxidation-Reduction; Oxygen; Photochemistry; Saudi Arabia; Sesquiterpenes; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured