Synthesis and pesticidal activities of new Quinoxalines

Authors: LIU, XING-HAI - Zhejiang University; YU, WEI - Zhejiang University; MIN, LI-JING - Zhejiang University; WEDGE, DAVID - Retired ARS Employee; TAN, CHENG-XIA - Zhejiang University; WENG, JIAN-QUAN - Zhejiang University; WU, HONG-KE - Zhejiang University; Cantrell, Charles; Bajsa-Hirschel, Joanna; HUA, XUE-WEN - Zhejiang University; DUKE, STEPHEN - Retired ARS Employee

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2020
Publication Date: 6/12/2020
Citation: Liu, X., Yu, W., Min, L., Wedge, D., Tan, C., Weng, J., Wu, H., Cantrell, C.L., Bajsa Hirschel, J.N., Hua, X., Duke, S.O. 2020. Synthesis and pesticidal activities of new Quinoxalines. Journal of Agricultural and Food Chemistry. 68:7324-7332. https://doi.org/10.1021/acs.jafc.0c01042.
DOI: https://doi.org/10.1021/acs.jafc.0c01042

Interpretive Summary: Natural products are a source of many novel compounds with biological activity for discovery of new pesticides and pharmacetuticals. Benzopyrazine (quinoxaline) is a fused N-heterocycle in many natural products. In the process of pesticide discovery, novel quinoxaline derivatives were designed and synthesized. Seven novel quinoxaline derivatives were synthesized via three steps. Pesticidal activities of these compounds were tested. Most of these compounds had herbicidal, fungicidal, and insecticidal activities. The herbicide activity of the these compounds might preclude them from being used on crop plants as fungicides or insecticides. The biological activities reported here are sufficient for further structure manipulation to improve their activity.

Technical Abstract: BACKGROUND: Natural products are a source of many novel compounds with biological activity for discovery of new pesticides and pharmacetuticals. Benzopyrazine (quinoxaline) is a fused N-heterocycle in many natural products. In the process of pesticide discovery, novel quinoxaline derivatives were designed and synthesized. RESULTS: Seven novel quinoxaline derivatives were synthesized via three steps. Pesticidal activities of these compounds were tested. Most of these compounds had herbicidal, fungicidal, and insecticidal activities. The compounds 2-(6-methoxy-2-oxo-3-phenylquinoxalin-1(2H)-yl)acetonitrile (3f) and 1-allyl-6-methoxy-3-phenylquinoxalin-2(1H)-one (3g) were the most active herbicides and fungicides. The energy and energy gap was calculated between the highest activity compound and lowest activity compounds by density functional theory (DFT) methods. CONCLUSION: Mode of action studies indicated that 3f is a protoporphyrinogen oxidase-inhibitiing herbicide. Compound 3f also possessed broad-spectrum fungicidal activity against plant pathogen Colletotrichum species. Some of these compounds also had insecticidal activity. DFT analysis can potentially be used to design more active compounds.