Photochemical hydroxylation of 1-methylanthraquinones: Synthesis of 9'-hydroxyaloesaponarin II

Triplet excited 9,10-anthraquinones can abstract H from alkyl groups ortho to the carbonyl. The hydrogen transfer results in a 1,x biradical which then undergoes a variety of reactions. One of these, oxidation of an alkyl substituent ortho to one of the carbonyls, was believed to go through formation of an endoperoxide. Photolysis of 1-methyl-9,10-anthraquinones using 419 nm light gave the corresponding suggested endoperoxide cleanly, supporting the hypothesis. Reduction of the endoperoxide resulted in oxidation of the ortho methyl group. The scope of the reaction was examined by using the photochemical hydroxylation in the first synthesis of a natural product, 9'-hydroxyaloesaponarin II.;DNA cleavers are important tools in molecular biology and medicine and they represent great candidates for photoactivated anticancer drugs. Anthracene is a tricyclic planar hydrophobic aromatic compound that can intercalate within DNA while substituents at the 9 or 10 position project into the grooves, where they would be ready to inflect the photo-inducible damage if properly substituted.;A number of anthracene analogues were therefore synthesized and their possible DNA photocleaving and anticancer abilities tested. The molecules were designed based on the known DNA photocleavage ability of intermediates in the Bergman cyclization or photo-Claisen rearrangements. While DNA cleavage was observed photolysis of candidate compounds under aerobic aqueous conditions resulted in anthraquinone formation. One of the compounds caused both ss and observed ds DNA photocleavage. The same compound showed a strong cytotoxic effect when photolysed with Zr75-breast cancer and Sklu-lung cancer cell lines. Singlet oxygen (1O2) scavengers inhibited both DNA ds photocleavage and photochemical conversion to anthraquinone completely. Taken together, the data suggested 1O2 intermediacy and the formation of an anthracene endoperoxide which could be responsible for the DNA photocleavage.;In chapter IV, photoenolization of o-substituted aryl aldehydes and their subsequent Diels-Alder reaction (PEDA) with acyl alkynes was attempted. Testing of the PEDA reactions as a possible bioorthogonal reaction in protein labeling was carried out. The experiments were designed in an attempt to examine the capability of the PEDA rection to chemically label proteins with fluorescent molecules that are generated in situ.