Synthesis And Antibacterial Activity Of Rosin-based Qxime Ester And Thiadiazole Derivatives

Rosin is a kind of worthful renewable resource and rosin acids are the main componentsof rosin. Rosin acids derivaties exhibit wide range of bioactivities and have importantapplication in the pharmaceutical and insecticide fields. In this thesis,15derivatives of oximeester, thiadiazole from rosin, disproportionated rosin and hydrogenated rosin were synthesizedthrough purification and chemical modification. In those compounds,10ones were newcompounds. Their structures were characterized by FTIR,~1H NMR, MS, Elemental Analysis,and Single Crystal X-ray Diffraction. The antimicrobial activity were estimated by theminimum inhibition concentration (MIC) method, and were compared to standardBromogeramine and Ampicillin Sodium.Six compounds including dehydroabietyl acetone oxime ester (2a), dehydroabietylbutanone oxime ester (2b), dehydroabietyl p-methylacetophenone ethanone oxime ester (2c),dehydroabietyl p-methoxy acetophenone ethanone oxime ester (2d), dehydroabietyl p-chloroacetophenone ethanone oxime ester (2e), and dehydroabietyl benzophenone oxime ester(2f) were synthesized through purification, acylating chlorination, oximation, and esterificationwith rosin as the starting material. The results showed that most derivatives displayedantibacterial activity. MIC of compounds2a,2b,2c,2d,2e and2f against Escherichia col were64,64,128,128,2and128μg/mL (lower than two references: Bromogeramine and AmpicillinSodium), respectively. MIC of compound2b against Klebsiella pneumonia and Escherichiaaerogenes were8and16μg/mL, lower than Bromogeramine and Ampicillin Sodium. MIC ofcompound2d against Klebsiella pneumonia was16μg/mL, lower than Bromogeramine andAmpicillin Sodium. The antibacterial activity was significantly affected by the benzene ringsubstituent position of the introducing group. The benzene ring para-position substituentposition of the compound was reduced the bacteriostatic activity. The different substituents haddifferent effects, with electron-withdrawing groups of compounds had strong antimicrobialeffects, and with electron-donating groups of compound antibacterial effect was poorer. Four compounds including5-dehydroabietyl-2-amino-1,3,4-thiadiazole (3a),5-dihydroabietyl-2-amino-1,3,4-thiadiazole (3b), acrylopimaric-di-[2-amino-1,3,4-thiadiazole](3c) and maleopimaric-di-[2-amino-1,3,4-thiadiazole](3d) were synthesized throughpurification, Diels-Alder dienes addition, and cyclization reaction with rosin, disproportionatedrosin and hydrogenated rosin as the raw material. The results indicated that these compoundsdisplay broad-spectrum antibacterial activity. Especially compound5-dehydroabietyl-2-amino-1,3,4-thiadiazole (3a) showed good antibacterial activity against Staphyloccocus aureu andStaphyloccocus epidermidis. MIC of compound3a were4and4μg/mL, lower thanBromogeramine or Ampicillin Sodium. The antibacterial activity of compounds may beinfluenced by the degree of functional groups. The compounds with small molecular skeletonshowed better antibacterial activity. The compounds containing benzene also showed betterbacteriostatic activity.Five compounds including2-benzamido-5-dehydroabietyl-1,3,4-thiadiazole (4a),2-phenyl ethyl amide-5-dehydroabietyl-1,3,4-thiadiazole (4b),2-p-methylbenzamido-5-dehydroabietyl-1,3,4-thiadiazole (4c),2-p-chlorobenzamido-5-dehydroabietyl-1,3,4-thiadiazole(4d) and2-p-nitrobenzamido-5-dehydroabietyl-1,3,4-thiadiazole (4e) were synthesized throughcyclization reaction, amidation with disproportionated rosin as the starting material. Singlecrystal of4b was obtained and its structure was analysized. crystal4b contained classicconfiguration of dehydroabietic group, three six-membered rings exhibited plane, half-chairand chair conformations, respectively. Three chiral carbon atoms exhibited R, S and Rconfigurations, respectively. The results indicated that MIC of compound4a againstPseudomonas aeruginosa was4μg/mL, lower than Bromogeramine and Ampicillin Sodium.The antibacterial activity was affected by the benzene ring side chain and benzene ringsubstituent position of introducing the group. The benzene ring para-position substituentposition of the compound was reduced the bacteriostatic activity.