Pest Management Science (2019) 75, 115-124

Taiyo Yokoi, Yoshiaki Nakagawa and Hisashi Miyagawa (2019)
Asymmetric synthesis of tetrahydroquinoline-type ecdysone agonists and QSAR for their binding affinity against Aedes albopictus ecdysone receptors
Pest Management Science 75 (1), 115-124
Abstract:
BACKGROUND
Tetrahydroquinolines (THQs) are a class of non-steroidal ecdysone agonists that specifically bind to mosquito ecdysone receptors (EcR). The THQ scaffold contains two chiral centers at the C-2 and C-4 positions, resulting in four stereoisomers. We have previously shown that the (2R,4S)-isomers are the most biologically active; however, the lack of a practical synthetic method for these isomers has hampered further structure–activity studies.
RESULTS
In this study, a chiral phosphoric acid-catalyzed Povarov reaction was employed to develop a facile asymmetric synthesis of THQs with a (2R,4S)-configuration, which allowed the preparation of a 40-compound library of enantiopure THQs. Evaluation of their binding affinity against Aedes albopictus EcR, followed by quantitative structure–activity relationship (QSAR) analyses, uncovered the physicochemical properties of THQs that are important for the ligand–receptor interaction. The most potent THQ derivative was twofold more active than the molting hormone, 20-hydroxyecdysone.
CONCLUSION
The QSAR results provide valuable information for the rational design of novel mosquito-specific ecdysone agonists.
(The abstract is excluded from the Creative Commons licence and has been copied with permission by the publisher.)
Link to article at publishers website
Database assignments for author(s): Yoshiaki Nakagawa

Research topic(s) for pests/diseases/weeds:
control - general

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Pest and/or beneficial records:

Beneficial	Pest/Disease/Weed	Crop/Product	Country	Quarant.
	Aedes albopictus