Synthesis and Insecticidal Activity of Some Novel Fraxinellone-Based Esters

In continuation of a program aimed at the discovery and development of natural products-based insecticidal agents, two series of novel fraxinellone-based esters were synthesized by modification at the C-4 or C-10 position of fraxinellone and evaluated for their insecticidal activity against the pre-third-instar larvae of Mythimna separata in vivo. An efficient method for the stereoselective synthesis of 4α-hydroxyfraxinellone from fraxinellonone was developed, and the steric configuration of <b>6h</b> was unambiguously confirmed by X-ray crystallography. Among 37 compounds, some derivatives displayed potent insecticidal activity; especially compounds <b>6h</b>, <b>6q</b>, <b>6t</b>, and <b>7q</b> showed more promising insecticidal activity than toosendanin, a commercial botanical insecticide derived from Melia azedarach. This suggested that introduction of the fluorine atom on the phenyl ring could lead to a more potent compound than one possessing chlorine or bromine. Meanwhile, introduction of the heterocyclic fragments at the C-4 or C-10 position of fraxinellone was essential for their insecticidal activity. This will pave the way for further design, structural modification, and development of fraxinellone as an insecticidal agent