Synthesis And Bioactivity Of Dehydroabietic Acid-based Five-membered Heterocyclic Compounds

Rosin is a renewable,natural and preponderant resource of China,and disproportionated rosin is one of the dominant varieties of modified rosin.As the most abundant component of disproportionated rosin,dehydroabietic acid is a diterpene resin acid which has phenanthrene skeleton,several chiral centres,and two reaction centres of carboxyl group and benzene ring,and is similar to many natural active compounds in structural skeleton.Dehydroabietic acid and its derivatives show a wide range of bioactivities.In recent years,it has become one of the research focuses for forest chemistry and chemistry of organic synthesis to synthesize bioactive compounds,especially heterocyclic compounds,through structural modification of dehydroabietic acid.In this thesis,the substructure connection method was applied to design and synthesize four types of novel dehydroabietic acid-based five-membered heterocyclic compounds with potential bioactivity by chemical modification of carboxyl group in dehydroabietic acid,and by introduction of bioactive 1,3,4-oxadiazole,1,3,4-thiadiazole,thiourea,sulfonamide,and amide groups into the molecular skeleton of dehydroabietic acid,using dehydroabietic acid as starting material.This research aims at providing a new way for the deep development and utilization of dehydroabietic acid.In this thesis,forty-three novel dehydroabietic acid-based five-membered heterocyclic compounds including one intermediate and forty-two target products were synthesized using dehydroabietic acid as starting material.The synthetic conditions were investigated preliminarily.The novel compounds were analyzed and characterized by means of 1H NMR,13C NMR,IR,MS,and elemental analysis.The single crystal of 9f was obtained by solvent evaporation method and its absolute configuration was determined by single crystal x-ray diffraction.Furthermore,fungicidal,herbicidal,plant growth regulating,and insecticidal bioactivities were evaluated for the novel compounds.The main research contens and results are shown as follows:1.Nine novel 5-dehydroabietyl-2-substituted amino-1,3,4-oxadiazoles 5a～5i were synthesized by cyclization of 1-dehydroabietacyl-4-substituted thiosemicarbazides 4a～4i under catalysis of mercuric acetate,using dehydroabietic acid as starting material.2.The intermediate 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6,which was not reported in literature,was prepared by one-pot method using dehydroabietic acid as starting material,followed by reaction of 6 with substituted isothiocyanates under catalysis of sodium hydroxide to afford eleven novel N-(5-dehydroabietyl-1,3,4-thiadiazol-2-yl)-N’-substituted thioureas 7a～7k.3.Eleven novel 5-dehydroabietyl-2-substituted sulfonamide-1,3,4-thiadiazoles 8a～8k were synthesized by reaction of the intermediate 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6 with a variety of substituted benzene sulfonyl chlorides,using dehydroabietic acid as starting material.4.Eleven novel 5-dehydroabietyl-2-substituted amide-1,3,4-thiadiazoles 9a～9k were synthesized by reaction of the intermediate 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6 with a series of substituted acyl chlorides,using dehydroabietic acid as starting material.The single crystal of 9f(R=2-ClC6H4)was obtained by solvent evaporation method as well.5.The fungicidal activity of all the novel compounds was evaluated by disc method in vitro.It was found that,at the concentration of 50 mg·L-1,the intermediate 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6 exhibited good fungicidal activity against Alternaria solani,Physalospora piricola,Cercospora arachidicola,and Gibberella zeae,and had inhibition rate of 88.9%against Alternaria solani.5-Dehydroabietyl-2-substituted amide-1,3,4-thiadiazoles 9a(R=C6H5)showed inhibition rate of 74.3%against Fusarium oxysporum f.cucumerinum.The other compounds only displayed weak inhibition activity against the five tested fungi.6.The herbicidal activity of all the novel compounds was evaluated by rape petri dish method and barnyard grass beaker method.It was found that,at the concentration of 100 mg·L-1,5-dehydroabietyl-2-substituted amino-1,3,4-oxadiazoles 5a～5i exhibited good growth inhibition activity against root of rape(Brassica campestris),in which compound 5d(R=4-CH3OC6H4)had the best inhibition rate of 74.6%.The other three typres of dehydroabietic acid-based five-membered heterocyclic compounds 7a～7k,8a～8k,and 9a～9k only showed weak growth inhibition activity against root of rape(Brassica campestris).All the novel compounds only displayed weak growth inhibition activity against barnyard grass(Echinochloa crusgalli(L.)).7.The plant growth regulating activity of 5-dehydroabietyl-2-substituted amino-1,3,4-oxadiazoles 5a～5i,5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6,and 5-dehydroabietyl-2-substituted amide-1,3,4-thiadiazoles 9a～9k was tested by cucumber cotyledon expansion method and wheat coleoptile section elongation method.The results showed that,at the concentration of 10 mg·L-1,these three types of compounds only displayed a certain cytokinin and auxin activity.8.The insecticidal activity of 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 6,N-(5-dehydroabietyl-1,3,4-thiadiazol-2-yl)-N’-substituted thioureas 7a～7k,and 5-dehydroabietyl-2-substituted sulfonamide-1,3,4-thiadiazoles 8a～8k was tested by leaf-dipped-method.It was found that,at the concentration of 200 mg·L-1,these three types of compounds exhibited good insecticidal activity against cotton bollworm(Helicoverpa armigera)and corn borer(Ostrinia nubilalis Hubner),in which compound 7a(R=C6H5)and 8a(R=C6H5)had control efficiencies of 93.3%and 90.0%,respectively,against cotton bollworm(Helicoverpa armigera),and 8a(R=C6H5)had control efficiency of 80.0%against corn borer(Ostrinia nubilalis Hubner).All the three types of compounds showed no insecticidal activity against diamondback moth(Plutella xylostella(L.))except for 7d(R=4-CH3C6H4).