Synthesis And Characterization Of The Piperazine Compounds And Their Biological Activity Determination

The main purpose of this study is to synthesis prochiral piperazine derivatives. To explore initially the conditions which transformed into chiral piperazine derivatives through microbial screening, to prove whether they have activity through bioactivity test; and to explore more synthesis routes for our following work.In this study, we used ethoxycarbonyl as a protection group, and chose acetophenone compounds (acetophenone, p-Methoxyacetophenone, p-fluoroacetophenone and 2,4-difluoroacetophenone) as piperazine prochiral group to synthesized a series of prochiral piperazine derivatives. At the same time we tested anticancer activity of the compounds such as 1-ethoxycarbonyl-4-acetophenonepiperazine dihydrobrohide. Moreover we initially explored the synthetic routes of many compounds such as 2-methylpiperazine, mandelic acid and 1-epoxypropylpiperazine.1. 20 compounds have been prepared in this thesis, 2 of which have never reported. 17 of them can be used for microbialtransformation from the point of structural analysis.2. As the method is simple, easy, and with relatively high yield, it is of good use in industry.3. A series of compounds such as 1-ethoxycarbonyl-4-acetophenonepiperazine dihydrobrohide have good inhibition ratio on human lung adenocarcinoma cell line A549, whose ID₅₀ were all within 37.5(umol/L). Especially 1-ethoxycarbonyl-4-(2,4 -difluoro-acetophenone)-piperazine dihydrobrohide is more active than any other compounds. The inhibition rate has reached 38.5% when the concentration is only 2.344μmol/L, and the more the concentration increase the more the inhibition rate increase quickly. Most cells were inhibited when the concentration is 9.375μmol/L. So some of these compounds have shown the potential value of anti-cancer medicinal. It may be able to improve the antitumor activity of pyridonecarboxylic acids. The results of this parts have never reported.4. Through the microbialtransformation, we got benzoic acid. But it was not the product which we expected. So further screening of microorganism is needed. We obtained one of the products through the alkaline hydrolysis method, but this method still not applicable because of the low yield. The acidic hydrolysis can be tested in futrue.5. 1-Acetyl-3-methylpiperazine, 1-Benzoyl-3-methylpiperazine, Ethylmandelate and 1-oxiranylmethylpiperazine etc. which we synthetized can all be used for microbialtransformation. These three routes are also promising.