Dissertation
Dissertation > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Antibiotics manufacture

Synthesis, Antifungal Activity and QSAR of Rosin-Based Quaternary Ammonium Salt Derivatives

Author LiangTao
Tutor LiShuJun
School Northeast Forestry University
Course Forest Chemical Process Engineering
Keywords rosin rosinyl quaternary ammonium salt Trametes versicolor Gloeophyllum trabeum QSAR
CLC TQ465
Type Master's thesis
Year 2013
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Rosin is renewable rich in resource in China, to be an important raw material applied in Fine. In this paper, rosin was used as the raw material for the synthesis of some kinds of rosinyl quaternary ammonium salt and rosinyl bis-quaternary ammonium salt derivatives with antifungal activity. Because of the existence of rosin phenanthrene ring, quaternary ammonium salt fungistats derived by rosin had some advantages of structure.Dehydrogenated rosin or tetrahydrogenated rosin was used as the raw material to reacted with excess epichlorohydrin(1:1.5, mole ratios) for3.5h at90degree Celsius, then reacted with tertiary amine with1%tetrabutyl ammonium bromide at85℃for3.5h, four quaternary ammonium salt products called N-(3-abietoxy-2-hydroxy) propyl-trimethyl/triethyl ammonium chloride were obtained, the yield were between70%and82%, another way was the intermediates reacted with secondary amine at85℃for3.5h and then reacted with epichlorohydrin again at90℃for3h, the two products were called N-(3-abietoxy-2-hydroxy) propyl-dimethyl/diethyl ammonium chloride. and the yield were67%and73%, respectively. The structure and purity of the target products were characterized by HPLC, IR and1HNMR. Antifungal activity was determined by filter paper method using Trametes versicolor and Gloeophyllum trabeum at0.025mmol/mL. The result showed that6rosinyl quaternary ammonium salt all have good antifungal activity to the fungi tested. And dehydroabietic base quaternary ammonium salts have better antifungal activity to Gloeophyllum trabeum, the inhibition zones were close to10, that approached it of dodecyl dimethyl benzyl ammonium chloride, which is one of commercially available quaternary ammonium salt type fungicide.Rosin acid was used as raw material to react with acrylic acid after high temperature processing to produce acrylpimaric acid, and the acrylpimaric acid after purification reacted with excess epichlorohydrin(1:3, mole ratios) for3.5h at90℃, then reacted with tertiary amine with1%tetrabutyl ammonium bromide at85℃for3.5h, two products called Bis-N-(3-hydroabietoxy-2-hydroxy) propyl-trimethyl/triethyl ammonium chloride were obtained, and the yield were71%and72%, respectively, another way was the intermediates reacted with secondary amine at85℃for3.5h and then reacted with epichlorohydrin again at90℃for3h, the two products were called Bis-N-(3-hydroabietoxy-2-hydroxy) propyl-dimethyl/diethyl ammonium chloride with the yield of65%and62%, respectively. The structure and purity of the target products were characterized by HPLC, IR and1HNMR. and the antifungal activity was determined by filter paper method using Trametes versicolor and Gloeophyllum trabeum at0.025mmol/mL. The result showed that four kinds of rosinyl bis-quaternary ammonium salt derivatives all had satisfactory antifungal activity, especially to Trametes versicolor, and four kinds of rosinyl bis-quaternary ammonium salts all had close anti-fungal activity to Gloeophyllum trabeum compared with dodecyl dimethyl benzyl ammonium chlorideComputer software Codessa2.7.16to determine the Quantitative Structure-Activity Relationship between rosinyl derivatives and the fungi of Trametes versicolor and Gloeophyllum trabeum using the data of different anti-fungal rate with filtering paper method. The best multi-linear regression method was used to confirm the best Quantitative Structure-Activity Relationship model via the breaking point of number of descriptors and its R2, the results showed that the best Quantitative Structure-Activity Relationship models of both the two fungi tested were the one with4descriptors. The result showed the correlation, inspection value and standard deviation were RTv2=:0.9722, FTv=166.33, sTv2=0.0014and RGt2=0.9736, FGt=175.19, SGt2=0.0026, respectively. The4descriptors of the best Quantitative Structure-Activity Relationship model to Gloeophyllum trabeum were Relative number of N atoms, ALFA polarizability(DIP), Avg nucleoph. react. index for a C atom and Polarity parameter/square distance. And the4descriptors of the best Quantitative Structure-Activity Relationship model to Trametes versicolor were Relative number of C atoms, Number of benzene rings, Final heat of formation/#of atoms and Max total interaction for a C-H bond. Internal validation and Leave one out method were used to check the calculated result. It showed that the R2, F and S2of the two checking methods all up to the standard. The final QSAR equation of the two fungi were ARTv=(-0.2561±0.0292)+(26.577±3.1575)×AnriC+(5.8131e-04±5.6260e-05)×Ap+(12.553±1.5193)×RnN+(0.2578±0.0709) x PPSD and ARGt=(3.4466±1.0492)-(10.811±0.88755) x RnC+(0.32136±0.0281) x Nbr+(0.1727±0.0182)×Fhf-(0.6318±0.0964)×MtiCHb.

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