Design, Synthesis, Crystal Structure, and Fungicidal Activity of L-Carvone Derivatives Containing an Oxime Ester Moiety

doi:10.6023/cjoc202010028

Abstract

L-Carvone is a natural product with fungicidal activity, which can be used as a lead compound for screening new fungicides. A series of L-carvone derivatives containing an oxime ester moiety were synthesized by splicing active substructure strategy with L-carvone as the lead compound. The structures of the L-carvone derivatives were characterized by IR, ¹H NMR, ¹³C NMR and HRMS analyses. The antifungal activities of these compounds were evaluated against five plant pathogenic fungi, namely Sclerotinia sclerotiorum, Fusarium graminearum, Pyricularia grisea, Fusariwn oxysporum and Thanatephorus cucumeris. The results indicated that most of the compounds showed good antifungal activities. Among them, (E)-2- methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-(4-ethylbenzoyl)oxime (4e) had the best fungicidal activity against Fusarium graminearum (EC₅₀=5.07 mg/L), and (S,E)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-(3-methylbenzoyl)oxime (4b) had the best fungicidal activity against Sclerotinia sclerotiorum, (EC₅₀=18.84 mg/L), which were better than the commercial fungicide enestroburin. Therefore, L-carvone derivatives have the potential to develop new fungicides.

Key words: nature product, L-carvone, synthesis, fungicidal activity

Cite this article

Can Jin, Xile Deng, Yong Zhou, Xiaomao Zhou. Design, Synthesis, Crystal Structure, and Fungicidal Activity of L-Carvone Derivatives Containing an Oxime Ester Moiety[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 2008-2018.

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Compd.	R	Inhibitory rate/%
Compd.	R	S. sclerotiorum	F. graminearum	P. grisea	F. oxysporum	T.cucumeris
4a	H	53.4	48.3	29.6	42.5	14.6
4b	3-CH₃	80.0	46.1	30.0	43.8	44.1
4c	4-CH₃	58.4	53.3	32.9	47.1	26.8
4d	2-CH₂CH₃	63.3	57.9	42.9	38.7	32.1
4e	4-CH₂CH₃	68.4	92.9	50.0	38.7	39.6
4f	4-CH(CH₃)₂	70.9	62.1	26.7	46.3	6.7
4g	4-C(CH₃)₃	57.1	62.9	33.3	46.2	22.1
4h	4-CH₂CH(CH₃)₂	39.1	69.6	28.8	45.6	10.5
4i	2-OCH₃	73.4	64.2	45.3	51.3	15.8
4j	3-OCH₃	41.2	66.7	30.8	38.8	11.7
4k	2-OCH₂CH₃	74.6	56.6	29.2	52.5	30.3
4l	4-OCH₂CH₃	62.9	83.3	31.7	57.5	10.4
4m	2-OCH₂CH₂CH₃	57.8	49.6	74.6	62.5	7.9
4n	2-Cl	45.3	48.8	28.3	47.5	7.8
4o	3-Cl	62.7	54.2	27.5	49.6	9.3
4p	4-Cl	41.6	82.9	36.7	44.1	10.4
4q	2,3-Cl	62.8	51.7	29.6	36.3	6.6
4r	2-Br	76.1	57.1	27.9	40.4	14.6
4s	3-Br	44.2	50.4	24.6	27.1	7.1
4t	4-Br	64.6	47.1	29.2	43.3	5.5
4u	2-F	58.3	67.5	28.7	38.3	20.4
4v	3-F	43.7	80.8	29.2	37.5	7.1
4w	4-F	44.6	83.1	42.1	51.7	11.7
4x	2,6-F	63.4	75.5	45.4	40.4	8.4
4y	4-CF₃	60.3	89.6	26.7	36.3	32.1
4z	4-NH₂	55.9	80.4	27.1	37.9	11.6
L-Carvone	—	32.9	57.7	22.3	35.3	8.3
Enestroburin	—	73.8	77.1	77.5	51.6	52.5

Compd.	R	Inhibitory rate/%
Compd.	R	S. sclerotiorum	F. graminearum	P. grisea	F. oxysporum	T.cucumeris
4a	H	53.4	48.3	29.6	42.5	14.6
4b	3-CH₃	80.0	46.1	30.0	43.8	44.1
4c	4-CH₃	58.4	53.3	32.9	47.1	26.8
4d	2-CH₂CH₃	63.3	57.9	42.9	38.7	32.1
4e	4-CH₂CH₃	68.4	92.9	50.0	38.7	39.6
4f	4-CH(CH₃)₂	70.9	62.1	26.7	46.3	6.7
4g	4-C(CH₃)₃	57.1	62.9	33.3	46.2	22.1
4h	4-CH₂CH(CH₃)₂	39.1	69.6	28.8	45.6	10.5
4i	2-OCH₃	73.4	64.2	45.3	51.3	15.8
4j	3-OCH₃	41.2	66.7	30.8	38.8	11.7
4k	2-OCH₂CH₃	74.6	56.6	29.2	52.5	30.3
4l	4-OCH₂CH₃	62.9	83.3	31.7	57.5	10.4
4m	2-OCH₂CH₂CH₃	57.8	49.6	74.6	62.5	7.9
4n	2-Cl	45.3	48.8	28.3	47.5	7.8
4o	3-Cl	62.7	54.2	27.5	49.6	9.3
4p	4-Cl	41.6	82.9	36.7	44.1	10.4
4q	2,3-Cl	62.8	51.7	29.6	36.3	6.6
4r	2-Br	76.1	57.1	27.9	40.4	14.6
4s	3-Br	44.2	50.4	24.6	27.1	7.1
4t	4-Br	64.6	47.1	29.2	43.3	5.5
4u	2-F	58.3	67.5	28.7	38.3	20.4
4v	3-F	43.7	80.8	29.2	37.5	7.1
4w	4-F	44.6	83.1	42.1	51.7	11.7
4x	2,6-F	63.4	75.5	45.4	40.4	8.4
4y	4-CF₃	60.3	89.6	26.7	36.3	32.1
4z	4-NH₂	55.9	80.4	27.1	37.9	11.6
L-Carvone	—	32.9	57.7	22.3	35.3	8.3
Enestroburin	—	73.8	77.1	77.5	51.6	52.5

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4e	4-CH₂CH₃	5.07	0.936	y=0.037x–0.187	0.32~8.65
4l	4-OCH₂CH₃	7.88	0.947	y=0.025x–0.200	1.47~12.61
4p	4-Cl	14.62	0.960	y=0.027x–0.392	9.87~18.89
4v	3-F	16.26	0.959	y=0.029x–0.469	12.03~20.28
4w	4-F	8.79	0.955	y=0.026x–0.225	2.67~13.41
4x	2,6-F	17.90	0.950	y=0.024x–0.437	13.02~22.69
4y	4-CF₃	7.92	0.946	y=0.033x–0.263	3.23~11.62
4z	4-NH₂	20.47	0.952	y=0.038x–0.786	9.56~34.50
Enestroburin	—	11.66	0.936	y=0.022x–0.261	5.23~16.73

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4e	4-CH₂CH₃	5.07	0.936	y=0.037x–0.187	0.32~8.65
4l	4-OCH₂CH₃	7.88	0.947	y=0.025x–0.200	1.47~12.61
4p	4-Cl	14.62	0.960	y=0.027x–0.392	9.87~18.89
4v	3-F	16.26	0.959	y=0.029x–0.469	12.03~20.28
4w	4-F	8.79	0.955	y=0.026x–0.225	2.67~13.41
4x	2,6-F	17.90	0.950	y=0.024x–0.437	13.02~22.69
4y	4-CF₃	7.92	0.946	y=0.033x–0.263	3.23~11.62
4z	4-NH₂	20.47	0.952	y=0.038x–0.786	9.56~34.50
Enestroburin	—	11.66	0.936	y=0.022x–0.261	5.23~16.73

Compd.	R	EC₅₀/(mg?L^–1)	R²	Regression equation	95% confidence limit
4b	3-CH₃	18.84	0.959	y=0.032x–0.595	9.45~28.84
4e	4-CH₂CH₃	26.11	0.949	y=0.025x–0.658	14.58~48.01
4f	4-CH(CH₃)₂	24.58	0.998	y=0.022x–0.551	16.29~31.17
4i	2-OCH₃	23.15	0.998	y=0.023x–0.529	17.33~25.50
4k	2-OCH₂CH₃	18.44	0.976	y=0.022x–0.411	13.11~29.07
4l	4-OCH₂CH₃	27.89	0.941	y=0.018x–0.500	20.84~36.84
4r	2-Br	25.34	0.995	y=0.023x–0.593	17.76~31.69
Enestroburin	—	23.31	0.961	y=0.029x–0.669	13.93~36.33

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