The Synthesis, Crystal Structures, Bioactivities And Properties Of Rotenone Oxime Derivatives

Structural diversity of natural products provided a library containing considerable lead compounds for pesticide researchers, so it is an important way to develop new pesticides using organic synthesis methods for structural optimization of the leading compounds. Rotenone is the principal active ingredient of Cube Resin used as an insecticide, belonging to the three major traditional botanical insecticides. Because of the photochemical degradation behavior and the low efficiency of pest control, it is difficult to be standardized and commercialized, and thus makes its application and promotion of great limitations. But it makes rotenone as highly potential for the development of green pesticides, for the advantages of the broad insecticide spectrum, not easy to produce drug resistance and helping to promote the ecological balance of environment. So reforming rotenone into the derivatives with high bioactivity and stability are currently in urgent need of solution research topics.In this study, on the base of the structure-activity relationships for the rotenone derivations, we introduced the oxime O-ether group, substituting C=N for C=O at 12 position, in order to reduce the acidity of the 12a-H and improve the stability of the whole molecular. Firstly, taking rotenone as the lead compound, we synthesis rotenone oxime by using the hydroxylamine hydrochloride reacts with 12-carbonyl of rotenone. Twenty-one rotenone oxime O-ether derivatives were synthesized by the etherification reaction using natural rotenone and a series of halids as substrates in alkaline conditions; Ten rotenone oxime esters derivatives were synthesized by the esterification reaction using natural rotenone and a series of chloride as substrates; Four rotenone oxime esters carbamate derivatives were synthesized by the reaction of rotenone oxime and a series of isocyanate. The effects of the solvents, microwaves were studied to the esterification reaction.Crystals of the compounds 4 and 33 suitable for X-ray analysis were obtained by slow evaporating a mixture solvent of ethanol and acetone at room temperature. And the corresponding stereochemistry assigned by X-ray crystallography show that rotenone derivatives retains the rotenone parent structure on the whole except for changing the dihedral angle of the V-shaped structure.The size of the angles follows the order: rotenone(105.30°) > compound 33(103.16°) > rotenone oxime (101.30°) > compound 4(99.35°); Besides, the changes of the substituents on 12 position caused the methoxy deviation from ring A. There are no obvious hydrogen bonds intermolecular of compound 4. But the hydrogen bonds exist between the proton of NH bond in one molecular and the C=O bond in another molecular from compound 33. Prevalence of Vanderwaals force further stabilizes the crystal structure.Potter-spraying method was used to measure the insecticidal activity of test compounds against M. separata. To measure the activities of test compounds against N. cincticeps, A. fabae and T. urticae, leaf-dipping method is introduced. In addition fungicidal activities of the title compounds against Gibberella zeae, Phytophythora capsici, Pyricularia oryzae, Botrytis cinerea, Sclerotonia sclerotiorum, Rhizoctonia solani and Erysiphe graminis were evaluated using the mycelium growth rate test. In particular, the preliminary biological activity tests show that disubstituted oxime ethers (compound 33) not only have general insecticidal and miticidal activity but also have a novel fungicidal activity against Rhizoctonia solani.In this paper, some active rotenone derivatives were selected to study the process of the photodegradation, through quantitative analyzing the residual products, using of high-performance liquid chromatography (HPLC) external standard method. The results show that the series of rotenone oxime ethers derivatives undergo the similar degradation trends to rotenone. And the DT50 for compound 23 was longer than rotenone (16 h). Compared to rotenone oxime O-ethers derivatives, the degradation process for rotenone oxime ester derivatives are more complex. At last, the lipid water partition coefficients for the derivatives were determined, using the method of HPLC, and this way overcomes the disadvantage of time-consuming operation and the poor reproducibility results from the traditional shake-flask method.