硫色酮甲酰胺衍生物的合成及其抑菌活性

doi:10.6023/cjoc202506027

摘要/Abstract

分别以2-氯苯乙酮和2-巯基苯甲酸为原料设计了两条合成路线, 合成了13个2-取代硫色酮甲酰胺衍生物. 利用平皿法研究了化合物对小麦全蚀病菌的抑制活性. 构效关系研究表明, 2-位取代基对化合物活性具有重要影响, 2-[(4-氯苯基)氨基]-N,N-二乙基-4-氧代-4H-硫色酮基-3-甲酰胺(6f)对小麦全蚀病菌具有较好的抑制活性, 在50 mg/L浓度下抑制率可以达到100%. 进一步研究结果表明4-(4-氧代-2-苯基-4H-硫色酮基-3-甲酰胺基)苯甲酸异丙酯(13e)对小麦全蚀病菌的抑制效果突出, 在12.5 mg/L浓度下抑制率亦可以达到100%, 其计算的EC₅₀值达到了0.07 mg/L的较低水平, 抑制活性超过了阳性对照硅噻菌胺(EC₅₀ 26.7 mg/L). 该研究将对活性化合物进一步结构设计与优化提供一定帮助, 为新农药的创制提供参考.

关键词: 硫色酮甲酰胺衍生物, 合成路线, 小麦全蚀病菌, 抑制活性

13 new thiochromone formamide derivatives substituted at position 2 were synthesized and two synthetic routes for these compounds were developed using 1-(2-chlorophenyl)ethanone and 2-mercaptobenzoic acid as materials, respectively. Their antifungal activities against Gaeumannomyces graminis var. tritici were evaluated in vitro by the plate method. The results of structure-activity relationship indicated that the group at position 2 of thiochromone formamide derivatives had an important influence on their antifungal activities against Gaeumannomyces graminis var. tritici. 2-(4-Chlorophenylamino)- N,N-diethyl-4-oxo-4H-thiochromene-3-carboxamide (6f) showed a good activity. Its inhibitory rate reached up to 100% at 50 mg/L. Further results showed that the activity of isopropyl 4-(4-oxo-2-phenyl-4H-thiochromene-3-carboxamido)benzoate (13e) against Gaeumannomyces graminis var. tritici was excellent. Its inhibitory rate also reached up to 100% at 12.5 mg/L with a lower value of EC₅₀ (0.07 mg/L) than positive control Silthiopham (EC₅₀ 26.7 mg/L). The results will provide some help for design of new active compounds and development of new fungicides.

Key words: thiochromone formamide derivative, synthetic routes, Gaeumannomyces graminis var. tritici, inhibitory activity

引用此文

周蒲, 苏子洋, 崔得运, 程绎南, 李毅, 周海峰, 孙炳剑, 李洪连. 硫色酮甲酰胺衍生物的合成及其抑菌活性[J]. 有机化学, 2026, 46(1): 87-95.

Pu Zhou, Ziyang Su, Deyun Cui, Yi-Nan Cheng, Yi Li, Haifeng Zhou, Bingjian Sun, Honglian Li. Synthesis of Thiochromone Formamide Derivatives and Their Antifungal Activities[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 87-95.

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图/表 7

图1. 活性化合物的结构设计

Figure 1. Structural design of proposed compounds

图式1. 目标化合物6a~6h的合成路线与结构

Scheme 1. Synthetic routes and structures of target compounds 6a~6h

图式2. 目标化合物13a~13e的合成路线与结构

Scheme 2. Synthetic routes and structures of target compounds 13a~13e

Entry	Base	T/℃	Time/h	Solvent	Yield/%
1	NaOH	130	8	DMF	13
2	NaOH	130	8	DMSO	15
3	NaOH	40	8	DMSO	35
4	NaH	130	8	DMSO	15
5	NaH	40	8	DMSO	57

表1. N,N-二乙基-2-乙硫基-4-氧代硫色酮-3-甲酰胺(4)的合成条件优化

Table 1. Optimization of conditions for synthesizing N,N-dieth- yl-2-ethylthio-4-oxo-4H-thiochromene-3-carboxamide

Entry	Promoter (1.6 equiv.)	Base (1 equiv.)	T/℃	Time/h	Solvent	Yield/%
1	—	K₂CO₃	r.t.	7	Toluene	0
2	PPh₃	—	r.t.	7	Toluene	Trace
3	PPh₃	C_S2CO₃	r.t.	7	Toluene	Trace
4	PPh₃	K₂CO₃	r.t.	7	Toluene	Trace
5	K₂CO₃	TMG	r.t.	7	Toluene	0
6	PPh₃	TMG	r.t.	7	Toluene	51
7	PPh₃	TMG	r.t.	7	DMF	Trace
8	PPh₃	TMG	r.t.	7	DMSO	Trace
9	PPh₃	TMG	50	7	Toluene	73
10	PPh₃	TMG	70	7	Toluene	57

表2. 4-羟基-2-苯基-3,4-二氢硫色烷-3-甲酸乙酯(10)的合成条件优化

Table 2. Optimization of conditions for ethyl 4-hydroxy-2- phenyl-3,4-dihydro-2H-thiochromene-3-carboxylate (10)

Compd.	Percent inhibition^a/% (in vitro)
Compd.	200 mg/L	100 mg/L	50 mg/L	25 mg/L	12.5 mg/L
6a	71.6	39.2	22.6	18.0	10.5
6b	87.0	80.9	67.3	50.4	41.3
6c	100	51.6	32.7	26.5	20.5
6d	99.1	62.9	39.8	20.7	3.8
6e	56.9	32.8	15.5	12.1	10.1
6f	100	100	100	70.6	29.2
6g	89.8	80.2	63.6	37.6	17.3
6h	97.4	90.8	88.6	86.6	57.6
13a	99.5	91.7	51.6	23.6	20.1
13b	58.3	44.9	28.9	23.3	17.5
13c	93.5	93.0	90.3	90.9	86.3
13d	98.6	93.0	87.0	87.8	80.6
13e	100	100	100	100	100
Silthiopham	100	92.3	66.7	40.5

表3. 2-取代的硫色酮甲酰胺衍生物的抑菌活性

Table 3. Inhibitory activities of 2-substituted thiochromone formamide derivatives

图2. 化合物13e不同浓度对小麦全蚀病菌的抑制活性

Figure 2. Inhibitory activity of 13e against Gaeumannomyces graminis var. Tritici y=0.8172x＋5.9993; R²=0.9688; EC50=0.07 mg/L. CK: control; 0.001, 0.01, 0.1, 1, 10 and 50 are the concentrations of compound 13e respectively (mg/L)

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