Design, Synthetic Method And Bioactivity Studies Of Tetronic Acid

Spirocyclic tetronic acid derivatives are novel pesticide developed by Bayer cropscience AG in the late ’90s. They are novel Acetyl CoA Carboxylase inhibitors. They disorder the energy metabolism of pest and make it death. Spirodiclofen, Spiromesifen and Spirotetramat are three representative commercial varieties. Because of their novel mode of action, they are always in the limelight. This text focuses on the study of their key step of synthesis and design novel structures. Based on the literatures, seven series novel Spirocyclic tetronic acid derivatives were synthesized. The target compounds were identified by’H NMR and element analysis or high resolution mass spectrum (HRMS), and their bioactivities were studied.4-Dimethylamine-pyridine (DMAP) is a frequently-used catalyst in acylation of tertiary alcohol or enol during our synthetic process. We discovered its hydrochloride can be used as recoverable catalyst for the first time. This catalyst can be used more than8cycles without activity lost. Its reaction mechanism was studied also; it may guide a novel kinetic resolution on racemic alcohols catalyzed by counterion composing with DMAP and chiral acid and the initial result was obtained.A series of novel spirocyclic tetronic acid derivatives containing oxalyl moiety were designed and synthesized. The results of bioassays indicated that most of the target compounds possessed excellent acaricidal activities against carmine spider mite larvae and eggs. Parts of the compounds showed higher activity than commercial Spiromesifen. Single-crystal structure study showed that the conformation was changed by introducing oxalyl and the conformations of compounds affect their activities heavily.The4-amino spirocyclic tetronic acid derivatives were designed and synthesized based on the study of metabolism of commercial variety. Alkyl, acyl, amino acid and amidine were introduced to amino group. The results of bioassays indicated that the bioactivities were changed a lot by introducing amino group. The target compounds exhibited herbicidal activity and bactericidal activity. Compound containing cyanamide group exhibited100%control of dicotyledonous weeds at first test. It can be studied as lead compound of herbicide.The spirocyclic tetronic acid compounds containing hydrazine and hydrazone group at4-position were designed and synthesized. The results of bioassays indicated that only compounds containing hydrazone group exhibited activities against lepidoptera pests. That means it is disadvantageous that introducing of water-solubility group into4position of tetronic acid.Naphthaline, phenoxy, phenamino and diphenyl ether were introduced into3-position of tetronic acid. The results of bioassays indicated that the activities were greatly lost by introducing naphthaline. That may explained by the steric hindrance of naphthaline. The conformations of the compound were change a lot by introducing phenoxy and phenamino, which lead to the activities lost. Interestingly, while diphenyl ether was introduced, unlike commercial varieties the target compounds exhibited activities against lepidoptera pests, bacterium and weeds. They can be further studied as lead compound of herbicide and fungicide.The further using of tetronic acid was limited by its rigidity. The4-hydroxy-isooxazoline analogues were designed and synthesized base on bioisosterism to overcome this problem. The results of bioassays indicated that all the target compounds exhibited good activities against lepidoptera pests and mite. Some of the compound exhibit herbicidal activity and bactericidal activity. The laws of different activities were not the same that means these compounds can be further studied as lead compounds of pesticide, herbicide and fungicide. This unique sight provides a new way for tetronic acid using as agricultural chemical.