Synthesis And Antimicrobial Activity Of Fumarate Based Sugar Easters

The relationship between structure and antimicrobial activity of food preservatives showed that a,β-unsaturated carbonyl is an effective bacteriostatic group. Dimethyl fumarate (DMF) is an effective preservative which contains two a,β-unsaturated carbonyl, but it is banned to be used in food because it can cause unpleasant odor, sublimation and skin allergy easily. So it is significant to study how to develop a new type of non-poisonous food preservative which can keep avoiding skin allergy and sublimation of DMF as well as making use of the a,β-unsaturated carbonyl group. The research indicates that by sugar molecules and methanol reacting with molecular fumarate, fumarate sugar ester compounds with excellent antibacterial activity could be obtained.In this paper by using d1-aspartic anhydride, methanol and galactose and so on as reactants galactosyl methy fumarate (GMF) was synthesized and its antibacterial activity was tested. With glucose, galactose, lactose, cellobiose, acetic anhydride, dl-aspartic acid anhydride, methanol as reactants, a series of acetylated fumarate sugar ester compounds were prepared. Then the strcture of these compounds was comfirmed by IR, HPLC. The main contents and some results have been listed as following:1. In order to synthesize galactosyl methy fumarate (GMF), the following route was adopted:monomethyl fumarate (MMF) was synthesized through mixing malefic anhydride with methanol and isomerizating with AICl3 firstly. Secondly MMF was reacted with SOCl2 to synthesis MMFC, then through esterification catalyzed by 4-dimethylaminopyridine (DMAP) to yield GMF.2. The ratio of MMFC to galactose was obtained by the effect on DE of GMF and growth adaptation period of milk microbe by adding GMF. Also other reaction parameters such as the dosage of acid binding agent and catalyst and reaction temperature and reaction time, etc. were obtained by mono-factor experiment, in which the yield and antibacterial activity of GMF were investigated as index marks. The results showed that the optimal synthetic conditions were:anhydrous K2CO3 was taken as acid binding agent and TBAB was taken as phase transfer catalyst, n(galactose)/n(MMFC)1/4, reaction temperature 45℃, reaction time 3 h. Under these optimal synthetic conditions, GMF (DE=1.66) with the color of light yellow was synthesized, which has the best antimicrobial activity. Measured by turbidimetry after adding GMF, the growth of milk microbe adaptation period was extended to 28 h that is the control of 7 times.3. Four kinds of acetylated fumarate sugar ester compounds were prepared through the following route:firstly sugar was reacted with acetic anhydride by perchloric acid as catalyst to synthesis full-acetyl sugar then bromination was taken at low temperature under dark conditions, finally target compounds were prepared by mixing acetylated sugar bromination with MMF by catalyst DMAP.4. The synthesis condition of acetylated fumarate sugar ester compounds was optimized and the result showed that when the ratio of MMF to acetylated sugar bromination was 1:1 and the amount of DMAP was 4% of the total quality of reactants, during temperature was 55℃and pH value 8-9 was kept with 4% KOH, also during the reaction process TLC detection was used to ensure acylation completely (The whole process needs 4 h～6 h).5. Anti-bacterial test results showed that acetyl fumarate sugar ester compounds had low antimicrobial activity on Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Saccharomyces cerivisiae and other strains tested. GMF (DE=1.66) whose anti-bacterial ability was close to MMF could remarkably inhibit the growth of the bacteria, mold and yeast on approval. Also, the activity did not influence by the pH value of environment. GMF is heat-resistant and would not cause skin allergy.