Study On Synthesis And Biological Activity Of Cinnamaldehydes Analogues

Cinnamaldehyde is the main component of the natural lauraceae cinnamon, which shows many bioactivities in current research, such as vasodilator, anti-platelet aggregation, anti-tumor, anti-bacterial, antifungal, anti-mutation activities and so on, and low toxicity. In this paper, a series of cinnamic aldehyde amino acid derivatives and substituted cinnamic aldehyde derivatives were designed and synthesized using cinnamic aldehyde as the precursor. The products were identified by IR, MS and 1HNMR and evaluated for their antifungal and antioxidant activities. Main contents of this research:1. Synthesis of cinnamic aldehyde amino acid schiff base potassium saltsAmino acids was added to the solution of potassium hydroxide in methanol to prepare amino acids potassium salt which reacted with cinnamaldehyde to produce imine compounds by the condensation of aldehyde and amino. The structure of imine is very similar with theα,β-unsaturated aldehyde, so these compounds may possess antiseptic and antibacterial activities. Fourteen cinnamaldehyde amino acid Schiff base potassium compounds were synthesized and characterized by IR, UV,1HNMR, elemental analysis.2. Synthesis of hydroxy-substituted cinnamaldehydesUnder the protection of acetic anhydride for the hydroxyl, hydroxy substituted benzaldehydes were condensed with malonic acid to obtain the hydroxyl substituted cinnamic acids which were transformed to acetoxy cinnamic acid chloride by SOCl2 as acylating reagents, deoxygenized to acetoxy cinnamic aldehyde by the reducing agent bis(triphenylphosphine) B cuprous hydride, and then de-protected by hydrolysis, purified by column chromatography to give target products hydroxy substituted cinnamic aldehyde. The structure of target compounds were identified by IR, MS, and1HNMR.3. the antibacterial activity of cinnamic aldehyde amino acid schiff base potassium saltAntibacterial activity of target compounds against E. coli, Bacillus subtilis, Saccharomyces cerevisiae was tested by filter paper method., Compounds respectively showed different inhibition to the three target bacterias in the 200 mg/L, and excellent activity in the 600 mg/L. Compound B possessed more significant activity than benzoic acid against Bacillus subtilis and Saccharomyces cerevisiae. In the concentration of 200 mg/L,400 mg/L,600 mg/L, the antibacterial circle diameters of Bacillus subtilis accordingly were 4.6 mm,8.7 mm,12.9 mm, and for Saccharomyces cerevisiae the antibacterial circle diameters were 4.5 mm,8.2 mm,12.6 mm. Compared with cinnamaldehyde and benzoic acid, the growth inhibitions of bacteria, yeast and milk rancidity bacteria of the compounds A and B at different pH were explored and analyzed. The growth of microorganisms were assayed at different times by measuring the increment, the results showed that at pH=4.5, in the 200 mg/L, cultured for 24 h, the strains grew slowly, and with the increase of pH value, antibacterial activity of compounds correspondingly decreased. In the bacterial tests, the inhibition of compounds A and B on gram-positive bacteria Bacillus subtilis was stronger than on Gram-negative bacteria E. coli, and compound B showed better inhibitory activity against the four strains than compound A.4. the antioxidant activity of hydroxyl substituted cinnamaldehydeA series of hydroxy-substituted cinnamaldehyde were designed and synthesized by hydroxy substituted benzaldehyde as a leading compound. The comparison of water-soluble hydroxyl cinnamic acid analogues and lipid-soluble hydroxyl cinnamaldehyde analogues for their effects on radical scavenging was assessed by 2,2-diphenyl-l-picrylhydrazyl (DPPH). Besides, the anti-haemolysis of compounds were assayed by testing the inhibition of human red blood cells hemolysis which induced by AAPH. From radical scavenging test, it showed the radical scavenging activity order of compounds on the DPPH was:H>D>C>VC>G>E>F>A>B. o-hydroxy and p-hydroxy cinnamic acid and o, p-hydroxy cinnamaldehyde displayed not so good free radical scavenging activity, the activity of ferulic was significantly better than ferulaldehyde, caffeic acid and coffee aldehyde manifested similar activity, and compounds H, D, C showed better radical scavenging activity than the antioxidant VC. According to the length of inhibition period, the anti-haemolysis of various compounds were ranked by the strong to weak:E>C>F>H>D>G>B>A> VC. Specially, compound E (Salicylic cinnamaldehyde) significantly prolonged the time of inhibiting hemolysis which emerged obvious dose relationship with the concentration.