(Z)-/(E)-胡椒酮基吡唑-肟酯化合物的合成及其抑菌活性研究

doi:10.3969/j.issn.0253-2417.2024.02.002

Abstract

Abstract:

Using piperitone as the raw material, 42 novel(Z)-/(E)-piperitone-based pyrazole-oxime ester(compounds 6a-6u, including 21 pairs of Z/E isomers) were synthesized through O-acylation reactions with substituted pyrazoles after carbonyl oximation. The structures of the target products were characterized using proton-1 nuclear magnetic resonance spectrum(¹H NMR), carbon-13 nuclear magnetic resonance spectrum(¹³C NMR), Fourier-transform infrared spectroscopy(FT-IR), and high-resolution mass spectrometry(HRMS). The Z/E configurations of the compounds were determined by single-crystal X-ray diffraction analysis(SC-XRD). In vitro bioactivity tests showed that the(Z)-/(E)-piperitone-based pyrazole-oxime ester compounds exhibited certain antifungal activities against eight plant pathogenic bacteria, including Fusarium oxysporum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoctonia solani, Bipolaris maydis, and Colleterichum orbiculare, at a mass concentration of 50 mg/L. The antibacterial activity was significantly influenced by the Z/E configurations of the compounds, and their activities against A. solani were found to be the most efficient. Wherein, (Z)-piperitone-based(3′, 5′-difluoromethyl)phenyl pyrazole-oxime ester((Z)-6o), (Z)-piperitone-based(p-trifluoromethyl)phenyl pyrazole-oxime ester((Z)-6u), (Z)-piperitone-based(p-nitro)phenyl pyrazole-oxime ester((Z)-6p), (E)-piperitone-based(p-nitro)phenyl pyrazole-oxime ester((E)-6p), (Z)-piperitone-based(p-trifluoromethoxy)phenyl pyrazole-oxime ester((Z)-6g), and(E)-piperitone-based(o-fluoro)phenyl pyrazole-oxime ester((E)-6i) exhibited the inhibition rates of 83.8%, 78.7%, 76.3%, 76.3%, 74.8%, and 74.3%, respectively, against A. solani. And compound(Z)-6u showed the inhibition rate of 82.5% against P. piricola, which was better than that of the positive control chlorothalonil. The three-dimensional quantitative structure-activity relationship(3D-QSAR) model(r²=0.928, q²=0.732) for the inhibitory activity of(Z)-piperitone-based pyrazole-oxime ester compounds against A. solani was established using comparative molecular field analysis(CoMFA) method.

Key words: piperitone, pyrazole, oxime ester, Z/E isomer, antifungal activity, 3D-QSAR

CLC Number:

TQ351

Wenjing ZHANG, Wengui DUAN, Guishan LIN, Yupei MENG, Zhaolei ZHANG, Xinyan LIU. Synthesis and Antifungal Activity of (Z)-/(E)-Piperitone-based Pyrazole-oxime Ester Compounds[J]. Chemistry and Industry of Forest Products, 2024, 44(2): 9-19.

Figures/Tables 8

Fig.1

Table 1

The antifungal rate of the target products against different strains(50 mg/L) %"

化合物 compounds	黄瓜枯萎病菌 F.oxysporum	花生褐斑病菌 C.arachidicola	苹果轮纹病菌 P.piricola	番茄早疫病菌 A.solani	小麦赤霉病菌 G.zeae	水稻纹枯病菌 R.solani	玉米小斑病菌 H.maydis	西瓜炭疽病菌 C.orbicaulare
(Z)-6a	24.3	32.5	22.5	60.3	43.5	22.2	20.5	25.8
(E)-6a	38.6	38.8	35.0	63.8	33.5	46.6	25.8	31.1
(Z)-6b	29.0	38.8	47.5	61.5	55.3	56.3	31.1	46.8
(E)-6b	19.5	26.3	22.5	47.5	45.3	27.1	15.3	25.8
(Z)-6c	33.8	41.3	30.8	59.6	75.0	22.2	36.3	31.1
(E)-6c	29.0	26.3	47.5	41.3	33.5	22.2	12.6	15.3
(Z)-6d	33.8	22.5	39.2	53.4	43.5	46.6	25.8	41.6
(E)-6d	67.6	41.3	35.0	70.0	48.2	39.3	25.8	36.3
(Z)-6e	43.3	53.8	35.0	47.5	58.2	78.8	36.3	41.6
(E)-6e	19.5	22.5	22.5	47.5	33.5	27.1	15.3	20.5
(Z)-6f	29.0	26.3	18.3	60.0	55.3	81.5	20.5	36.3
(E)-6f	43.3	45.0	30.8	76.3	48.2	61.5	36.3	36.3
(Z)-6g	19.5	45.0	43.3	74.8	49.4	81.5	36.3	72.1
(E)-6g	14.8	32.5	47.5	47.5	45.3	22.2	20.5	31.1
(Z)-6h	24.3	35.0	22.5	55.0	68.2	32.0	25.8	41.6
(E)-6h	24.8	77.7	27.9	62.9	77.2	20.6	33.6	35.0
(Z)-6i	33.8	41.3	22.5	59.1	51.2	46.6	25.8	25.8
(E)-6i	43.8	48.5	27.7	74.3	52.2	71.6	33.1	33.2
(Z)-6j	19.5	38.8	35.0	56.7	48.2	32.0	15.3	25.8
(E)-6j	22.2	53.2	40.1	62.3	51.1	25.3	22.0	25.6
(Z)-6k	62.9	57.5	43.3	64.9	45.3	61.5	31.1	36.3
(E)-6k	19.5	45.1	22.5	70.0	33.5	22.2	15.3	25.8
(Z)-6l	67.6	74.0	35.0	58.8	51.2	56.3	36.3	52.1
(E)-6l	33.8	51.3	22.5	66.3	64.1	51.5	31.1	36.3
(Z)-6m	43.3	41.3	30.8	61.8	33.5	46.6	20.5	31.1
(E)-6m	33.8	22.5	22.5	47.5	48.2	34.4	31.1	36.3
(Z)-6n	24.3	45.0	22.5	66.5	68.2	34.4	20.5	25.8
(E)-6n	33.8	51.3	30.8	76.3	64.1	46.6	31.1	41.6
(Z)-6o	38.6	16.3	18.3	83.8	45.3	27.1	31.1	25.8
(E)-6o	43.3	28.8	43.3	63.8	48.2	41.7	25.8	25.8
(Z)-6p	19.5	28.8	18.3	76.3	51.2	34.4	20.5	20.5
(E)-6p	52.9	35.0	30.8	76.3	51.2	56.3	46.8	46.8
(Z)-6q	38.6	51.3	22.5	23.1	42.4	39.3	20.5	25.8
(E)-6q	29.0	32.5	22.5	63.8	33.5	22.2	12.6	31.1
(Z)-6r	24.3	45.0	22.5	58.9	68.2	22.2	15.3	25.8
(E)-6r	19.5	45.0	26.7	47.5	57.1	22.2	15.3	15.3
(Z)-6s	33.4	44.0	26.2	55.5	35.0	22.2	25.2	28.1
(E)-6s	19.5	51.3	43.3	47.5	39.4	22.2	15.3	25.8
(Z)-6t	33.8	45.0	35.0	70.0	74.1	32.0	25.8	25.8
(E)-6t	33.8	51.3	43.3	70.0	60.0	46.6	25.8	25.8
(Z)-6u	24.8	48.5	82.5	78.7	37.8	30.0	35.5	45.7
(E)-6u	67.6	41.3	22.5	70.0	45.3	61.5	31.1	31.1
百菌清 chlorothalonil	100.0	73.3	75.0	73.9	73.1	96.1	90.4	91.3

Table 1

Fig.2

Table 2

Fig.3

Fig.4

Fig.5

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化合物compound	CoMFA值CoMFA value	E_D	E′_D	残差residue
(Z)-6a(R=H)	174	-2.435	-2.422	-0.013
(Z)-6b(R=o-Br)	176	-2.488	-2.464	-0.024
(Z)-6c(R=m-F)	174	-2.466	-2.448	-0.018
(Z)-6d(R=m-Cl, p-CH₃)	188	-2.605	-2.604	-0.001
(Z)-6e(R=m-CH₃)	184	-2.674	-2.584	-0.090
(Z)-6f(R=m-Br)	180	-2.515	-2.567	0.052
(Z)-6g(R=p-OCF₃)	188	-2.224	-2.252	0.028
(Z)-6h(R=m, p-CH₃)	196	-2.558	-2.605	0.047
(Z)-6i(R=o-F)	172	-2.475	-2.483	0.008
(Z)-6j(R=m, m-CH₃)	186	-2.528	-2.538	0.010
(Z)-6k(R=o, m-CH₃)	194	-2.378	-2.355	-0.023
(Z)-6l(R=o, p-CH₃)	194	-2.490	-2.447	-0.043
(Z)-6m(R=m-OCH₃)	186	-2.438	-2.491	0.053
(Z)-6n(R=p-Br)	182	-2.393	-2.377	-0.016
(Z)-6p(R=p-NO₂)	182	-2.153	-2.226	0.073
(Z)-6r(R=m, p-Cl)	184	-2.526	-2.514	-0.012
(Z)-6s(R=m-Cl)	176	-2.555	-2.561	0.006
(Z)-6t(R=p-I)	184	-2.364	-2.367	0.003
(Z)-6u(R=p-CF₃)	188	-2.115	-2.077	-0.038

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Synthesis and Antifungal Activity of (Z)-/(E)-Piperitone-based Pyrazole-oxime Ester Compounds

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