Studies On Design, Synthesis And Properties Of Inhibitors Of The Target Enzyme

Pyruvate dehydrogenase complex is already known to be a site of pesticide action. In order to obtain higher herbicidally and fungicidatly active new phosphonate derivative with commercial potential, One approach to design a inhibitor of pyruvate dehydrogenase with a novel structure by using biochemical reasoning was attempted. The study of 3D-QSAR, quantum chemistry and then optimizing the structure by chemical modification were carried out on the basis of the study of synthesis, mechanism, biochemistry and biological activities test, alpha-(Substituted phenoxy acetoxy)alkyl phosphonates(or phosphinates)(or monometal salts)with good herbicidal activities and fungicidal activities as lead compound have been founded and demonstrated as a kind of inhibitors of pyruvate dehydrogenase complex. Pyrido-pyrimidine compounds have still been found to show widespread biological activities. Some of them have been used as herbicides, fungicides, pesticides and medicine. The compounds have been demonstrated as a kind of inhibitors of the target ALS enzyme. In this dissertation, about thirteen kinds containing one hundred and sixty-seven unreported compounds were synthesized and confirmed by elemental analysis, 1H NMR, 31P NMR, 13C NMR, OC-MS, LC-MS, IR, ICP and X-ray crystal structure diffraction. The general formulas of these compounds are as following:A simple and efficient procedure for synthesis of methyl- a -(2,4-dichlorophenoxyacetoxy) Alkyl phosphonates(or phosphinates)monometal salts is described. This method was applied to the synthesis of novel phosphonate(or phosphinates) derivatives containing sensitive groups to acid, base or water such as carboxylate ester.The cyclization of carbodiimide with HY in presence of base was studied.The reactions of pyridinyl-4-methanimidamide with varies of N-H were studied. A reasonable mechanism was put forward to explain this reaction.The crystal structure of four a -oxyphosphonates(or monosodium salts) was determined analyzed. Abnormality in 1H NMR of the compounds was explained by X-ray crystal structure diffraction.The biological activities of one hundred and sixty-seven unreported compounds were studies. The results showed that most of them display obviously herbicidal activities and fungicidal activities.The results showed that most of them display obviously herbicidal activities and fungicidal activities. The compound ID-16 which selected from live potted plant tests appeared to have sufficient commercial potential. The results of the study encourage the view that biochemical design of agrochemicals will be successful.The results of the quantum chemistry suggested that the difference of bond length, charge and dipole moment of the compounds resulted in their herbicidal activities.Using the data of the crystal structure of ID-16, twenty-three n a -oxyphosphonate monometal salts were investigated aiming at developing a three-dimensional quantitative structure-activity relationship model using the CoMFA technique. According to the CoMFA results, we optimized molecular structures and predicted their activities. It provided further information for our molecular design in inhibitor of pyruvate dehydrogenase with potential high herbicidal activity.