Study On The Synthesis Of A Novel Anticancer Dicopper(Ⅱ) Complex And The Anti-HIV Drug Intermediate CAPIC

Design, synthesis, structure and property of functional molecules based on DNAinteractions have gotten extended interests for their playing an important role in the design,synthesis and mechanism of drug. Acquired Immune Deficiency Syndrome （AIDS） hasbeen one of the most serious diseases in the world since it was found in1981. Therefore, toresearch new anti-HIV drugs with low prices became a vital task that should beaccomplished by the government and researchers as soon as possible.This theisi aims at finding anticancer and antibacterial metal complexes targeting DNAwith high activity and low toxicity. A novel dissymmetrical N,N’-bis（substituted）oxamideligand,N-（5-chloro-2-hydroxyphenyl）-N’-[3-（2-hydroxyethylamino）propyl]oxamide （H3oxpep）, and its binuclear copper（II） complex,[Cu₂（oxpep）（phen）] ClO₄, were synthesized andcharacterized. The interactions of H3oxpep and [Cu₂（oxpep）（phen）]ClO₄with HS-DNAwere investigated by using absorption and emission spectrometry and viscometry. Theresults suggested that both of the two compounds can interact with HS-DNA in the mode ofintercalation with the intrinsic binding constants of6.67×104M-1and4.50×105M-1. In vitroanticancer activities of H3oxpep and [Cu₂（oxpep）（phen）]ClO₄were tested by SRB assaysagainst human hepatocellular carcinoma cells SMMC-7721and human lungadenocarcinoma cells A549. And [Cu₂（oxpep）（phen）]ClO₄has the better cytotoxic activitiesthan those of H3oxpep.Nevirapine is a non-nucleoside reverse transcriptase inhibitor that has been establishedto be clinically useful for the treatment of infection by HIV. In recent years, the research onthe synthesis of2-chloro-3-amino-4-methylpyridine （CAPIC） which is a key intermediatein the production of Nevirapine has been gaining more and more attention. In this paper, theevolvements about the synthesis of CAPIC are introduced and summarized. And, based onthese summaries, its synthetic method is improved and optimized.2-cyanoacetamide and4,4-dimethoxyl-2-butanone were used as raw materials. After condensation, cyclization,cholorination, hydrolysis and Hofmann reaction, CAPIC was synthesized with a total yield62.01%.