Synthesis And Bioactivity Of Heterocyclic Compounds Based On Modification Of The Carboxyl Group And B Ring In Dehydroabietic Acid

Rosin is a natural and preponderant biomass resource of China.Dehydroabietic acid is a constituent of rosin,and also the dominant component of disproportionated rosin.Dehydroabietic acid and its derivatives have been found to show a wide range of bioactivities.In this thesis,four types of novel dehydroabietic acid-based multifunctional bioactive compounds were designed and synthesized by chemical modification of the carboxyl group and B ring in dehydroabietic acid,and by introduction of bioactive 1,3,4-thiadiazole,phosphonate,thiazolidinone,thiazole,amide,and thiourea groups into the molecular skeleton of dehydroabietic acid,using dehydroabietic acid isolated from disproportionated rosin as starting material.This study aims at providing a new approach for the deep development and utilization of dehydroabietic acid.In this thesis,four types of novel dehydroabietic acid derivatives,comprising sixty-seven target compounds,were synthesized.The synthetic conditions were investigated preliminarily.Structural characterization of the novel compounds were carried out by spectrographic methods of FT-IR,1H NMR,13C NMR,ESI-MS and 31P NMR.Furthermore,antifungal,herbicidal,and antitumor activities were evaluated for the target compounds.The main research contents and results are shown as follows.1.Seventeen novel dehydroabietic acid-based 1,3,4-thiadiazole-a-amino phosphonate compounds 3a-3q were synthesized by the Mannich-type reaction of 2-amino-5-dehydroabietyl-1,3,4-thiadiazole 2 with a series of substituted benzaldehydes and triphenyl phosphate,using dehydroabietic acid as starting material.2.Sixteen novel dehydroabietic acid-based 1,3,4-thiadiazole-thiazolidinone compounds 6a-6p were synthesized through the intermediates of 5-dehydroabietyl-2-amino-1,3,4-thiadiazole 2,5-dehydroabietyl-2-chloro-acetamino-1,3,4-thiadiazole 4,and 5-dehydroabietyl-1,3,4-thiadiazole-thiazolidinone 5,using dehydroabietic acid as starting material.3.Twenty novel dehydroabietic acid-based B ring-fused-thiazole-amide compounds 11a-11t were synthesized through the intermediates of methyl dehydroabietate 7,7-carbonyl methyl dehydroabietate 8,6-bromo-7-carbonyl methyl dehydroabietate 9,and dehydroabietic acid-based B ring-fused-thiazole-amine 10,using dehydroabietic acid as starting material.4.Fourteen novel dehydroabietic acid-based B ring-fused-thiazole-thiourea compounds 12a-12n were synthesized through the intermediates of methyl dehydroabietate 7,7-carbonyl methyl dehydroabietate 8,6-bromo-7-carbonyl methyl dehydroabietate 9,and dehydroabietic acid-based B ring-fused-thiazole-amine 10,using dehydroabietic acid as starting material.5.The antifungal activity of the target compounds was evaluated by disc method in vitro against the five plant pathogens.It was found that,at the concentration of 50 ?g·ml-1,dehydroabietic acid-based 1,3,4-thiadiazole-?-aminophosphonate compounds 3e(R=o-F)and 3f(R=p-F)showed prominent inhibition activity against Cercospora arachidicola with respective inhibition rates of 96.9%and 93.8%,which was better than that of the positive control azoxystrobin.Compounds 3h(R=m-MeO),3a(R=o-Br),3c(R=o-Cl)and 3e(R=o-F)exhibited prominent inhibition activity against Physalospora piricola with inhibition rates of>95.0%,which was better than or close to that of the positive control azoxystrobin.Compounds 3e(R=o-F),3h(R=m-MeO),and 3i(R=p-MeO)displayed outstanding inhibition activity against Alternaria solani with inhibition rates of>95.0%,which was better than that of the positive control azoxystrobin.Dehydroabietic acid-based 1,3,4-thiadiazole-thiazolidinone compounds 6c(R=p-F),6f(Ro-Br),and 6n(R=m-OCH3)showed excellent inhibition activity against Gibberella zeae with inhibition rates of?91.3%,which was identical to that of the positive control azoxystrobin.Compounds 3e(R=o-F)and 3h(R=m-MeO)are leading compounds worthy of further investigation.6.The herbicidal activity of the target compounds was evaluated by rape petri dish method and barnyard grass beaker method.It was found that,at the concentration of 100 ?g·ml-1,most of the target compounds did not show obvious herbicidal activity,and only dehydroabietic acid-based B ring-fused-thiazole-amide compounds 11c(R=p-CIC6H4)and llq(R=amyl)exhibited growth inhibition activity of about 50%against root of rape(Brassica campestris).7.The antitumor activity of dehydroabietic acid-based 1,3,4-thiadiazole-?-aminophosphonate compounds 3a-3q was evaluated at the concentration of 20?M by MTT method against MGC803(gastric cancer cell),BEL-7404(hepatocellular cancer cell),A549(lung adenocarcinoma cell),Hela(uterine cervical cancer cell),and Hepg2(hepatocellular carcinoma cell).Compounds 3a(R=o-Br),3c(R=o-Cl),and 3k(R=o-NO2)showed a certain antitumor activity.