Synthesis of Thiochromone Formamide Derivatives and Their Antifungal Activities

doi:10.6023/cjoc202506027

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 87-95.DOI: 10.6023/cjoc202506027 Previous Articles Next Articles

ARTICLES

硫色酮甲酰胺衍生物的合成及其抑菌活性

周蒲^a, 苏子洋^a, 崔得运^b, 程绎南^a^,^*(), 李毅^a, 周海峰^a, 孙炳剑^a, 李洪连^a

^a 河南农业大学植保学院郑州 450046
^b 河南省科学院高新技术研究中心郑州 450002

收稿日期:2025-06-20 修回日期:2025-08-18 发布日期:2025-09-23
基金资助:
河南省重点研发专项(251111111600); 河南省高等学校重点科研计划(25A210014); 以及河南省科学院高层次人才科研启动(241802037)

Synthesis of Thiochromone Formamide Derivatives and Their Antifungal Activities

Pu Zhou^a, Ziyang Su^a, Deyun Cui^b, Yi-Nan Cheng^a^,^*(), Yi Li^a, Haifeng Zhou^a, Bingjian Sun^a, Honglian Li^a

^a Plant Protection College, Henan Agricultural University, Zhengzhou 450046
^b High & New Technology Research Center of Henan Academy of Sciences, Zhengzhou 450002

Received:2025-06-20 Revised:2025-08-18 Published:2025-09-23
Contact: * E-mail: chyn212@aliyun.com
Supported by:
Key R&D Special Project of Henan Province(251111111600); Key Research Project Plan for Higher Education Institutions in Henan Province(25A210014); High-Level Talent Research Start-Up Project Funding of Henan Academy of Sciences(241802037)

1. .pdf(2739KB)

Abstract

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

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 7

References 20

[1]	Freeman J.; Ward E. Mol. Plant Pathol. 2004, 5, 235.
[2]	Bateman G. L.; Gutteridge R. J.; Jenkyn J. F.; Self M. M. Ann. Appl. Biol. 2008, 152, 243. doi: 10.1111/aab.2008.152.issue-2
[3]	Phillion D.; Wong S. C.; Shortt B. US 5486621, 1996.
[4]	Yun Y. Z.; Yu F. W.; Wang N.; Chen H. G.; Yin Y. N.; Ma Z. H. Pest Manage. Sci. 2012, 68, 1156. doi: 10.1002/ps.v68.8
[5]	Xie G.; Jin W.; Zhao Y.; Cheng Y.; Sun B.; Sun S.; Wang M.; Wei D.; Li H. Chin. J. Org. Chem. 2014, 34, 1124 (in Chinese). doi: 10.6023/cjoc201401036
	(谢桂英, 靳文波, 赵艳芹, 程绎南, 孙炳剑, 孙淑君, 汪梅子, 位丹丹, 李洪连, 有机化学, 2014, 34, 1124.) doi: 10.6023/cjoc201401036
[6]	Jin W.; Xie G.; Sun S.; Zhao Y.; Cheng Y.; Sun B.; Li H. Chin. J. Org. Chem. 2014, 34, 2376 (in Chinese). doi: 10.6023/cjoc201406006
	(靳文波, 谢桂英, 孙淑君, 赵艳芹, 程绎南, 孙炳剑, 李洪连, 有机化学, 2014, 34, 2376.) doi: 10.6023/cjoc201406006
[7]	Phillion D. P.; Braccolino D. S.; Graneto M. J.; Phillips W.; Van Sant K. A.; Walker D. M.; Wong S. C. EP 538231, 1993.
[8]	Phillips W. G.; Mao M. K.; Ma C.; Fevig T. WO 9962915, 1999.
[9]	Huan X.; Wang Y.; Peng X.; Xie S.; He Q.; Zhang X.; Lan L.; Yang C. Eur. J. Med. Chem. 2022, 236, 114309. doi: 10.1016/j.ejmech.2022.114309
[10]	Xiao T.; Chen G. C.; Hu B. CN 108003133, 2016.
[11]	Holshouser M. H.; Loeffler L. J.; Hall I. H. J. Med. Chem. 1981, 24, 853. pmid: 7277393
[12]	Dhanak D.; Keenan R. M.; Burton G.; Kaura A.; Darcy M. G.; Shah D. H.; Ridgers L. H.; Breen A.; Lavery P.; Tew D. G.; West A. Bioorg. Med. Chem. Lett. 1998, 8, 3677. pmid: 9934494
[13]	Mi P.; Tan Y.; Ye S.; Lang J.; Lv Y.; Jiang J.; Chen L.; Luo J.; Lin Y.; Yuan Z.; Zheng X.; Lin Y. Eur. J. Med. Chem. 2024, 263, 115956.
[14]	Hirao I.; Yamaguchi M.; Terada T.; Hasebe K. Bull. Chem. Soc. Jpn. 1985, 58, 2203. doi: 10.1246/bcsj.58.2203
[15]	Tao J.; Tuck T. N.; Murphy G. K. Synthesis 2016, 48, 772. doi: 10.1055/s-00000084
[16]	Li X.; Ze X.; Zhou S.; Hu Z.; He C.; Jia Y.; Liu L.; Wang T.; Li J.; Xu S.; Yang D.; Chen Z.; Yao H.; Xu J.; Yao H. J. Med. Chem. 2023, 66, 5118. doi: 10.1021/acs.jmedchem.3c00058
[17]	Li P.; Wu Y.; Zhang T.; Ma C.; Lin Z.; Li G.; Huang H. Beilstein J. Org. Chem. 2019, 15, 703. doi: 10.3762/bjoc.15.65
[18]	Li M.; Petersen J. L.; Hoover J. M. Org. Lett. 2017, 19, 638. doi: 10.1021/acs.orglett.6b03806
[19]	Nguyen T. T. H.; Nguyen T. X.; Cao T. T. T.; Dinh T. H.; Nguyen H. H.; Bui T. T. T.; Pham V. P.; Mac D. H. Synlett 2017, 28, 429. doi: 10.1055/s-0036-1588377
[20]	Wang L.; Zhang Y.; Wang D.; Wang M.; Wang Y.; Feng J. J. Agric. Food Chem. 2018, 66, 81. doi: 10.1021/acs.jafc.7b03913

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

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

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

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

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

硫色酮甲酰胺衍生物的合成及其抑菌活性

Synthesis of Thiochromone Formamide Derivatives and Their Antifungal Activities

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 7

References 20

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Fangxia Lin, Zhihong Wang, Decai Dai, Xueming Zhou, Luyong Wu. Two New Shikimic Acid Derivatives from the Flower of Trachycarpus fortunei [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1248-1251.
[2]	Jing-Yu Yang, Min-Min Tang, Li Chen, Xin-Yi Lai, Xin Zhuo, Xue-Ming Zhou, Guang-Ying Chen. Study on the Secondary Metabolites of Endophytic Penicillium sclerotiorum HLL113 [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 896-900.
[3]	Zirong Zeng, Mengmeng Zhang, Hong Wang, Jia Li, Yuewei Guo, Mingzhi Su. Chemical Constituents of Sinularia nanolobata from the South China Sea [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 891-895.
[4]	Jing Cong, Fang Fang, Liangmin Xue, Meng Wang, Chao Tian, Xiaowei Wang, Junyi Liu, Zhili Zhang. Synthesis and Antitumor Activity of Novel Pyrimidine Monocyclic Nonclassical Antifolates [J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 776-787.
[5]	He Mei, He Chaofan, Liu Ling, Ye Jiao, Hu Aixi, Chen Yun, Xu Lujie, Liu Ailin. Synthesis, Crystal Structure and Neuraminidase Inhibitory Activity of 1,2,4-Triazole-3-sulfide Derivatives [J]. Chinese Journal of Organic Chemistry, 2020, 40(8): 2402-2410.
[6]	Mei Rongqing, Huang Guolei, Wang Bin, Bai Meng, Luo Youping, Chen Guangying, Zheng Caijuan. Two New Isocoumarins Isolated from a Mangrove-Derived Fungus Penicillium citrinum HL-5126 [J]. Chin. J. Org. Chem., 2019, 39(5): 1479-1482.
[7]	Tang Xuemei, Fan Li, Zhang Zechao, Yang Dacheng. Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit [J]. Chin. J. Org. Chem., 2019, 39(5): 1460-1468.
[8]	Shi Lei, Xu Jingjing, Bi Jingjing, Zhang Zhiguo, Liu Tongxin, Yang Xiaolan, Zhang Guisheng. Synthesis and Biological Activity of Benzo[h]quinolinium Hydrazine Compounds [J]. Chin. J. Org. Chem., 2018, 38(11): 3016-3025.
[9]	Fan Yaqin, Zhu Guoliang, Wang Yi, Zhu Xiaocui, Gong Qianhong, Jia Qian, Fu Peng, Zhu Weiming. α-Pyronoids with Quorum Sensing Inhibitory Activity from the Mangrove Fungus Penicillium camemberti OUCMDZ-1492 [J]. Chin. J. Org. Chem., 2018, 38(10): 2798-2804.
[10]	Yang Ningning, Kong Fandong, Ma Qingyun, Huang Shengzhuo, Luo Duqiang, Zhou Liman, Dai Haofu, Yu Zhifang, Zhao Youxing. Chemical Constituents from the Cultures of Fungus Xylaria polymorpha [J]. Chin. J. Org. Chem., 2017, 37(4): 1033-1039.
[11]	Zhang Wenbo, Shi Danshu, Zhang Chunzhen, Yu Zhiguo. Two New Rhabduscin Analogues from Xenorhabdus bovienii SN52 [J]. Chin. J. Org. Chem., 2017, 37(4): 996-999.
[12]	Mei Wenwen, Guo Yuewei, Li Jia, Cai Meiyi, Ma Wenquan, Gong Jingxu, Wang Xuedong. Synthesis and Protein-Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Indolepropyl Based 1,3,4-Oxadiazole Derivatives [J]. Chin. J. Org. Chem., 2016, 36(3): 533-539.
[13]	Cheng Yinan, Jin Wenbo, Xie Guiying, Ma Yichao, Zhao Yanqin, Li Honglian. Synthesis of Thiophene Formyl Thiourea Derivatives and Fungicidal Activity [J]. Chin. J. Org. Chem., 2016, 36(11): 2683-2688.
[14]	Chen Yanchi, Ren Yujie. Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues [J]. Chin. J. Org. Chem., 2015, 35(5): 1123-1130.
[15]	Xie Guiying, Jin Wenbo, Zhao Yanqin, Cheng Yinan, Sun Bingjian, Sun Shujun, Wang Meizi, Wei Dandan, Li Honglian. Synthesis of Thiophene Carboxamide Derivatives and Inhibitory Activity against Gaeumannomyces graminis var. tritici. [J]. Chin. J. Org. Chem., 2014, 34(6): 1124-1131.