Parallel Synthesis And Screening Of Pyrethroid And β-elemene Derivatives

A random heterocyclic pyrethroid library and a structure-optimizedβ-elemene library were designed,combinatorially constructed and screened.Combining two kinds of active skeletons of chyramthemic acids andnitrogen-containing heterocycles, a 357 compounds pyrethroid library wasconstructed using parallel synthesis.The screening results showed that the compounds in the pyrethroidlibrary had no obvious pesticidal activities. A few compounds were foundexellent fungicidal activities with ED₅₀ < 0.1×10^-6 in vitro test, and thelibrary showed better perfomace on phytophthora infestans (PHYTIN) andalternaria solani (ALTESO) on tomato than on the other targets ingreenhouse test. The most important is that 5 compounds were found potentto be lead compounds for optimization of fungicidal activity by BayerCropScience's test. Except for good herbicidal activities being found insome compounds, the best performance comes from a compound withinhibition percentage over 90% against all 6 kinds of herbicidal targets.Morever, we found those different kinds of chyramthemic acid or differentpositions of hydroxyl-or amino-substituted group on heterocycle distinctlyvaried biological activities of the compounds.In the design of ?-elemene library, we used a bridge sturcture with tworeaction centers to derive ?-elemene, which was proved to be an efficientmethod. In our library construction, a key piperazine intermediate readilypurified from two isomers was used to build the library of ?-elemenederivatives using combinatorialsynthesis. Eight kinds of enzymes were selected to screen the ?-elemene library.Most of compounds in the library have biological activities higher than?-elemene. This distinctive effect appeared in human macrophage elastase(HME) test. The screening results showed that five compounds haveinhibition percentages over 80% against HME, and the best performancewas up to 91.6% which was far higherthan ?-elemene and the intermediate. After SAR study, we found the bioactivities of acylation derivatives of?-elemene were generally higher than that of alkylation derivatives in theHME test.