Synthesis, Characteration And Properties Of Amino Substituted Anthraquinones And Their Intermediates

The substituted anthraquinone as bioreductive drug has become one of the most hotspot in the field of the anticancer research for their outstanding properties of antitumor drugs. In this paper, a series of amino substituted anthraquinones were designed and synthesized on the basis of bioreductive drugs acting mechanism.The intermediates 5-chloro-1,4-dihydroxyanthraquinone, 6-chloro-1,4-dihydroxyanthra -quinone, 5,8-dichloro-1,4-dihydroxyanthraquinone and 5,6,7,8-tetrachloro-1,4-dihydroxy -anthraquinone were prepared according to Friedel-Crafts reaction.The relation between the structures of chlorophenylanhydride with their acylating activity was studied. Meanwhile, the effect of reactive conditions such as reactive temperature and the amount of catalyst on the yield of products were also examed in this paper. It is shown that, the dominant factor is conjugate effect of chlorine in chlorophenylanhydride. The difference of the position and the amount of chlorine lead to the difference of reactive conditions and the difficult degree of those reactions.The active intermediates leuco-5-chloro-1,4-dihydroxyanthraquinone, leuco-6-chloro-1,4 -dihydroxyanthraquinone and leuco-5,6,7,8-tetrachloro-1,4-dihydroxyanthraquinone were produced by reducing reaction. In those reactions, the effect of different reducing agents and methods on the yield of products were investigated. Farthermore, the reactive conditions were optimized.1,4-Bis[[(2-dimethylamino)ethyl]amino]-5,8dihydroxyanthraquinone, 1,4-bis[[2-[(2 -hydroxyethyl)amino]ethyl]amino]-5,8-dihydroxyanth-raquinone, 1,4-bis[[(2-dimethylamino) -ethyl]amino]anthraquinone and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraqui -none were synthesized. All those compounds above were characterized by IR and 1HNMR, etc.Some of compounds which were synthesized in this paper were tested in vitro antitumor test. The results show that the compounds 1,4-bis[[(2-dimethylamino)ethyl]amino] -5,8-dihydroxyanthraquinone and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraqui -none exhibit good effect on inhibition of vitro cancer cells.The routes and technics of synthesis of antitumor drug-AQ4 have been researched in this paper. Also, the high yield and high purity of the product was obtained by optimized reactive conditions. As a result, a simple and practical route was provided in this paper.