Study On New Method Of Spermine Preparation

Polyamine is a kind of fatty amine, which is essential for keeping normal physiological function of cells. It is being in most of lives. Since the polyamine being found in last century, great progress in research on synthesis and application of it has been achieved.Spermine is one of the polyamine, which was found by Anton von Leeuwenhoek in human sperm in 1677. Decades of research on the biological activities of spermine showed that it play an important role in cell division processes of life. Being polycation at physiological pH, it binds tightly to and strongly modulates the biological activities of anionic cellular components. Due to these and other findings, many researchers have being explored synthesis and application of spermine and its derivative used as chemotherapeutic agents.Based on the reported researches, we design a new synthesis route from cheap saccharin to Spermine tetrahydrochloride.Saccharin was alkylated by 1,4-dichlorobutane and 1,6-bis(o-acyl-benzenesulfonyl) -1,6-diazahexane (I) was obtained. It was investigated that the factors of influencing the alkylation reaction such as catalyst,the ratio of raw material, temperature, feeding method etc.. Reaction of anhydrous saccharin and 1,4-dichlorobutane in the ratio of 2.5 in the presence of potassium iodide(about 10% of saccharin in mass) at 110°C for 6 hours gave (I) in the yield of 96.5%.The (I) was hydrolyzed in 10% alkaline aqueous solution and N,N'-bis((o- hydroxylformyl)-benzenesulfonyl)-1,4-butyenediamine (II) was obtained. The yield of (II) is about 91.8%.Compound (II) was reacted with acrylonitrile in the presence of sodium hydroxide obtaining 4,9-bis(o-hydroxylformyl)-benzenesulfonyl)-4,9-diazalaurodinitrile(III). Influence of temperature, ratio of raw material, reaction time, etc. had been researched. In the optimized condition(Ratio of acrylonitrile to II is 6 (in mole); Reaction time, 10 hours; Reaction temperature, 15°C; Solvent: 5% alkaline aqueous solution), The yield of (III) is 83.2%.5,10-bis((o-hydroxylformyl)-benzenesulfonyl)-1,5,10,14-tetraazatetradecane (IV) was obtained by hydrogenation of (III) in the presence of Raney Ni and Pd-charcoal at 50°C for 48 hours. The ratio of Pd-charcoal to III and Raney Ni to III are 1/10 (in mass) and 1/2 (in mass) respectively.Spermine tetrahydrochloride(V) was produced by hydrolysis of compound (IV) in the 20% hydrochloric acid for 2 h. The total yield of Spermine tetrahydrochloride in the base of 1,4-dichlorobutane is more than 27%.There are five steps in the new procedure. All of the step can be run in mild condition with good yield. In addition, the raw material, saccharin and 1,4-dichlorobutane are very cheap, and the catalyst and the solvent can be recovered. So, production of Spermine tetrahydrochloride in the manner is not costly. Therefore, the procedure is a new applicable synthesis method for preparing sperminme in industrialized scale.