| Sarcoptes scabiei var. cuniculi is one of the parasites can serious damage the health of rabbit, which often leads to an infectious sarcoptidosis. The body weight of nfected rabbit markedly decreased, and even death. It makes the breeding of rabbit suffer substantial losses. In previous study had found a new kind of esters derivatives named octadecanoic acid-3,4-furanodiyl ester which was isolated from chloroform extract of neem oil. It possessed potent acaricidal activity against S.scabiei var. cuniculi larvae. However the compound has many shortcomings. For example, the extraction yield, solubleness and synthetic yield of octadecanoic acid-3,4-furanodiyl ester is totally poor.Howadays, the research of octadecanoic acid-3,4-furanodiyl ester focus on the acaricidal activity, bacteriostatic activity and the preliminary mechanism of those activity. There is no literature reported regarding the structure-function relationship and structure modification of this compound. In order to determined the structure-function relationship and acaricidal active group of octadecanoic acid-3,4-furanodiyl ester. This research selected a suitable esterification method and modified the structure of octadecanoic acid-3, 4-furanodiyl ester. To obtain a series of its derivates and intermediate products that evaluated their acaricidal activity.1. The modification of octadecanoic acid-3,4-furanodiyl ester’carbon chain: This research used the chloride esterification synthesis to modify the carbonate carbon chain part of octadecanoic acid-3,4-furanodiyl ester and taking 3,4-tetrahydrofuran glycol as raw material and pyridine as catalyzer. Then the mixture react with Heptadecanoic acid, palmitoyl chloride, tetradecanoyl chloride, lauroyl chloride, neodecanoyl chloride, octanoyl chloride, hexanoyl chloride, butyryl chloride, acetyl chloride. When finish all of the reaction, three stable derivatives of octadecanoic acid-3,4-furanodiyl ester was obtained:compound a and b and c, all of them are white crystalline solid and their productive rate were 28%,63%and 76%, respectively.IR,’H-NMR,13C-NMR, MS analysis showed that compound a is Heptadecanoic acid acid-tetrahydrofuran-3,4-diyl ester, compound b is Palmitic acid acid-tetrahydrofuran-3,4-diyl ester, compound c is Myristic acid-tetrahydrofuran-3,4-diyl ester.2. The modification of octadecanoic acid-3,4-furanodiyl ester’furan ring:This research added lipid soluble group, ether-base, into the furan ring of octadecanoic acid-3, 4-furanodiyl ester. D-ribose was used as raw material, by protecting the hydroxyl group, then took off the methylol of 2 and using the 3-allyl bromide to replace the hydroxyl of 5, the next step was removing the hydroxyl protection group and then the mixture react with palmitoyl chloride, tetradecanoyl chloride, lauroyl chloride, neodecanoyl chloride, octanoyl chloride, hexanoyl chloride, butyryl chloride, acetyl chloride were happened. A white crystalline solid was obtained and IR, H-NMR,13C-NMR, MS analysis were used to analyze the intermediate products and derivative. Results showed that compound 1 was 6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d] [1,3]dioxol-4-ol,the productive rate was 89%. Compound 2 was 2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol,the productive rate was 93%. Compound 3 was 4-(allyloxy)-2,2-dimethyltetrahydrofuro[3,4-d][l,3]dioxole, the productive rate was 46%. Compound 4 was 2-(allyloxy) tetrahydrofuran-3,4-diol, the productive rate was 91%. compound 5 was (3S,4S)-2-(allyloxy)tetrahydrofuran-3,4-diyl diheptanoate, the productive rate was 40%.3. Acaricidal activity of octadecanoic acid-tetrahydrofuran-3,4-diyl ester derivatives in vitro:The result shows that:The transformation of carbon chain obtained three derivatives of octadecanoic acid-tetrahydrofuran-3,4-diyl ester. The S.scabiei var.cuniculi treated by those compounds, compounds c 55.67 min started effect, all the S.scabiei var.cuniculi died when treated 870.00 min. Followed by compounds b and a, start time of were 109.67 min and 180.67 min, all the death of 1070.00 min and 1070.00 min. Acaricidal activity for compound 5 was worst, the start time of was 370.00 min, all the death was 2880.00 min. Compound a’s LC50 is 13.528 mg/mL. the LC50 of compound b is 6.144 mg/mL,the LC50 of compound c is 5.134 mg/mL, compounds 5’s LC50 is 4.411 mg/mL. The results proved that the acaricidal activity of compound c match with ivermectin, and beyond octadecanoic acid-tetrahydrofuran-3,4-diyl ester, compound b and a have acaricidal activity. Compound 5 has poor acaricidal activity.Synthesis of octadecanoic acid-tetrahydrofuran-3,4-diyl ester intermediate’s acaricidal activity:The acaricidal activity of compound 1, compound 2 and compound 4 showed significantly, the start time of death were 9.17 min and 6.00 min and 22.00 min, all the death time of 176.00 min,55.67 min and 452.00 min. Compounds 3a and 3b’s acaricidal effect is not significant.The LC50 of compound 1 is 3.955 mg/mL, the LC50 of compound 2 is 1.031 mg/mL, compounds 3a’s LC50 is 2.500 mg/mL, LC50 of compound 3b is 1.601 mg/mL, LC50 of compound 4 is 0.828 mg/mL. The results proved that compounds 1 and 2 have remakable acaricidal activity, which superior to ivermectin.Compound 4 also has good acaricidal activity, its acaricidal effect and was equal to that of ivermectin.The results above showed that octadecanoic acid-tetrahydrofuran-3,4-diyl ester after optimization of carbon chain structure, shorten the length of the carbon chain, the corresponding acaricidal activity increase remarkable but did not significantly. It can guess that the main acaricidal activity groups of octadecanoic acid-tetrahydrofuran-3,4-diyl ester structure is furan ring. By introducing ether furan ring base has not increased the acaricidal activity. Synthesis of the intermediate have obtained good acaricidal activity. |
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