Tetrahydroquinoline (THQ)-type compounds are a class of ecdysone agonists and potential larvicides against mosquitoes. The structure-activity relationships (SAR) of these compounds were previously investigated (Smith et al., BMCL, 2003, 13, 1943-1946), and one of the cis-forms (2R, 4S) was reported to be stereoselectively synthesized. However, convincing data regarding the stereochemistry of this compound was not reported. In this study THQ-type compounds were synthesized according to the published method, and were submitted for X-ray crystal structure analysis. This analysis revealed that two enantiomers are packed into the crystal form as a racemic mixture. We separated these enantiomers via chiral HPLC, and the absolute configurations of each enantiomers were determined by X-ray crystallography. Each of the enantiomers was tested for mosquito larvicidal activity in vivo and competitive binding to the ecdysone receptor in vitro. Compared to the (2S, 4R) enantiomer, the (2R, 4S) enantiomer showed 55 times higher activity in the larvicidal assay, and 36 times higher activity in the binding assay.

Structural requirement and stereospecificity of tetrahydroquinolines as potent ecdysone agonists

248th National Meeting (2014)

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