Design and synthesis of small molecular 2-aminobenzoxazoles as potential antifungal agents against phytopathogenic fungi

Abstract

Graphic abstract In order to discover novel antifungal agents, three series of simple 2-aminobenzoxazole derivatives were designed, synthesized and evaluated for their antifungal activities against eight phytopathogenic fungi. The in vitro antifungal results showed that most of the target compounds exhibited excellent and broad-spectrum antifungal activities to all the tested fungi. Particularly, the six compounds 3a , 3b , 3c , 3e , 3m and 3v displayed the most potent antifungal activity, with EC 50 value of 1.48–16.6 µg/mL, which were much superior to the positive control hymexazol. The in vivo study further confirmed that compounds 3a , 3c , 3e and 3m displayed good preventative effect against Botrytis cinerea at the concentration of 100 µg/mL. The structure–activity relationships research provides significant reference for the further structural optimization of 2-aminobenzoxazole as potential fungicides. Forty-four 2-aminobenzoxazole derivatives were designed and synthesized as agricultural antifungal agents, the in vitro and in vivo antifungal experiments showed that compounds 3a , 3b , 3c , 3e , 3m and 3v exhibited excellent and broad-spectrum antifungal activities compare with the commercial fungicide hymexazol. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10213-7.

Natural Products‐Based Fungicides: Synthesis and Antifungal Activity against Plant Pathogens of 2H‐Chromene Derivatives

“…As outlined in Scheme 1, compounds 1a – o were prepared by condensation of substituted phenol and 3‐chloro‐3‐methyl‐1‐butyne with CuCl 2 ‐DBU as a catalyst, and further cyclization by heating at 120 °C in pyridine [16] . Then, compound 1c was oxidized using Pinnick oxidation reaction to give the natural product Anofinic acid ( 1p ), [17] and C‐5‐alkyl‐substituted 2 H ‐chromene derivatives ( 1q ‐ y ) were successfully synthesized by Suzuki cross‐coupling reaction [13] . As described in Scheme 2, various of chromene‐chalcone hybrid compounds ( 2a – h ) were obtained by Claisen‐Schmidt condensation of 1k and substituted benzaldehydes.…”

“…General Procedure for the Synthesis of Compounds 1qy [13] To a mixture of 1n (0.2 mmol), K 2 CO 3 (0.6 mmol), substituted boronic acids (0.4 mmol), Pd(PPh 3 ) 4 (0.01 mmol) and 1,4-dioxane/H 2 O (1 : 1, 4 mL) in a round flask, the mixture was heated at 80 °C for 8 -24 h under argon atmosphere. After 1n was consumed, the mixture was evaporated and purified by silica gel column chromatography to afford the title compounds 1q -y .…”

“…Encouraged by above mentioned results and in continuation of our program aimed at the discovery and development of high‐efficacy and broad‐spectrum antifungal candidates, [9–13] herein we have designed and synthesized four series of 2 H ‐chromene derivatives as potential fungicides. As shown in Figure 2, firstly, in order to explore the electronic effects and space effects on the antifungal activity, compounds 1a – y containing various substituted on the chromene skeleton were designed by the principle of homologue derivation.…”

Crystallization, structural study and analysis of intermolecular interactions of a 2-aminobenzoxazole–fumaric acid molecular salt

“…Benzoxazole derivatives are important heterocyclic compounds that exhibit a broad range of biological activities, including antibacterial (Paramashivappa et al, 2003), antimicrobial (Erol et al, 2022), antitumor (Imaizumi et al, 2020), anti-inflammatory (Parlapalli et al, 2017), analgesic (Ali et al, 2022;Sattar et al, 2020), antitubercular (S ˇlachtova ´et al, 2018), herbicidal (Sangi et al, 2019) and fungicidal (Fan et al, 2022). 2-Aminobenzoxazoles have been found to act as ligands for the internal ribosome entry site (IRES) RNA of the hepatitis C virus (HCV) (Rynearson et al, 2014).…”

Design, Synthesis, Computational Docking and Biological Evaluation of Novel 4-Chloro-1,3-Benzoxazole Derivatives as Anticancer Agents

“…The basic aim of the synthetic and medicinal chemistry was to synthesize the compounds that results in high yields with greatest purity and show excellent activity as therapeutic agents with minimal toxicity. Eminent among these are anti-histaminic [3] , antifungal [4] , cyclooxygenase Inhibiting [5] , anti-tumor [6] , antiulcer [7] , anticonvulsant [8] , hypoglycemic [9] , antiinflammatory [10,11] , anti-tubercular activity [12] , anti-parasitics [13] , herbicidal [14] , antiviral [15] , antiallergic and anthelmintic activities [16] . Also, they have a number of optical applications such as photoluminescents, whitening agents and in dye lasers [17] and are also used as organic brightening agents and organic plastic scintillators [18] .…”