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Title: Structural requirement and stereospecificity of tetrahydroquinolines as potent ecdysone agonists.
Authors: Kitamura, Seiya
Harada, Toshiyuki
Hiramatsu, Hajime
Shimizu, Ryo
Miyagawa, Hisashi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-8597-3201 (unconfirmed)
Nakagawa, Yoshiaki  kyouindb  KAKEN_id
Author's alias: 中川, 好秋
Keywords: Tetrahydroquinoline
Ecdysone
Stereospecificity
Mosquito
Larvicide
Issue Date: 1-Apr-2014
Publisher: Elsevier Ltd.
Journal title: Bioorganic & medicinal chemistry letters
Volume: 24
Issue: 7
Start page: 1715
End page: 1718
Abstract: Tetrahydroquinoline (THQ)-type compounds are a class of potential larvicides against mosquitoes. The structure-activity relationships (SAR) of these compounds were previously investigated (Smith et al., Bioorg. Med. Chem. Lett. 2003, 13, 1943-1946), and one of cis-forms (with respect to the configurations of 2-methyl and 4-anilino substitutions on the THQ basic structure) was stereoselectively synthesized. However, the absolute configurations of C2 and C4 were not determined. In this study, four THQ-type compounds with cis configurations were synthesized, and two were submitted for X-ray crystal structure analysis. This analysis demonstrated that two enantiomers are packed into the crystal form. We synthesized the cis-form of the fluorinated THQ compound, according to the published method, and the enantiomers were separated via chiral HPLC. The absolute configurations of the enantiomers were determined by X-ray crystallography. Each of the enantiomers was tested for activity against mosquito larvae 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 mosquito larvicidal assay, and 36 times higher activity in the competitive receptor binding assay.
Rights: © 2014 Elsevier Ltd.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/187052
DOI(Published Version): 10.1016/j.bmcl.2014.02.043
PubMed ID: 24630413
Appears in Collections:Journal Articles

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