5‐Membered Mesoionic Insecticides: Synthesis and Evaluation of 1,3,4‐Thiadiazol‐4‐ium‐2‐olates with High Affinity for the Insect Nicotinic Acetylcholine Receptor

The vast majority of drugs and agrochemicals contain heterocyclic ring systems, which impact ease of synthesis, speed of compound derivatization, and protein target site binding, as well as uptake, transport and many other properties. Mesoionics are unique compact heterocyclic structures with an aro...

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Bibliographic Details
Published in:European journal of organic chemistry 2019-09, Vol.2019 (31-32), p.5527-5531
Main Authors: Kuzmina, Olesya M., Weisel, Martin, Narine, Arun A.
Format: Article
Language:English
Subjects:
Affinity
Agrochemicals
Heterocycles
In vivo methods and tests
Insecticides
Insects
Mesoionic compounds
Neonicotinoids
Organic chemistry
Proteins
Quantum chemistry
Receptors
Synthesis
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Summary:The vast majority of drugs and agrochemicals contain heterocyclic ring systems, which impact ease of synthesis, speed of compound derivatization, and protein target site binding, as well as uptake, transport and many other properties. Mesoionics are unique compact heterocyclic structures with an aromatic and highly polarized character. The design and synthesis of 5‐membered mesoionic thiadiazol‐4‐ium‐2‐olates with high insecticidal activity and potent in vitro affinity on insect nicotinic acetylcholine receptors (nAChRs) is described. Modelling experiments using a known acetylcholine‐binding protein as surrogate for the insect nAChR showed interactions with the thiadiazoliumolate that were consistent with that expected for related insecticides. Quantum chemical, photostability, greenhouse residual, as well as plant systemicity studies were conducted to understand the in vitro and in vivo behavior of this novel class of insecticides. Mesoionic thiadiazoliumolates were found to be potent competitive modulators of the insect nicotinic acetylcholine receptor and showed high levels of insecticidal activity against a small set of agriculturally relevant insect pest species.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201900637