Synthesis and Antifungal Activity of 3-Aryl-7-methyl- 7-hydroxy-2-octen-6-olide

doi:10.6023/cjoc202101049

Abstract

In order to optimize the structure of 3-phenyl-7-methyl-7-hydroxy-2-octen-6-olide, the synthesis of racemic and optical 3-aryl-7-methyl-7-hydroxy-2-octen-6-olides has been achieved via epoxidation-lactonization procedure and Sharpless asymmetric dihydroxylation as the key steps in 61%~91% yields, respectively. Their structures were fully characterized by IR, ¹H NMR, ¹³C NMR, and HRMS data. Their antifungal activities were evaluated, and it showed that (R)-3-phenyl-7-methyl- 7-hydroxy-2-octen-6-olide (5a) was the most active compound with the EC ₅₀ values in the range of 0.2~13.5 µg/mL against the tested six phytopathogens, better than its ( S)-isomer and racemic mixture. It would be the potential lead structure to be optimized. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compounds (S)-5a, 5d and 5j had a significant impact on the structure and function of the hyphal cell wall of S. sclerotiorum mycelium.

Key words: 3-aryl-7-methyl-7-hydroxy-2-octen-6-olide, epoxidation-lactonization, asymmetric dihydroxylation, antifungal activity

Cite this article

Weiwei Wang, Yu Zhao, Xinlei Liu, Jiazhen Jiang, Ming'an Wang. Synthesis and Antifungal Activity of 3-Aryl-7-methyl- 7-hydroxy-2-octen-6-olide[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2343-2353.

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Entry	Ar	Olefin acid	Lactone	Yield/%
1	C₆H₅	1-13a	5a	80
2	2-ClC₆H₄	1-13b	5b	91
3	3-ClC₆H₄	1-13c	5c	84
4	4-ClC₆H₄	1-13d	5d	69
5	4-CH₃OC₆H₄	1-13e	5e	61
6	4-CH₃C₆H₄	1-13f	5f	75
7	4-FC₆H₄	1-13g	5g	70
8	4-CF₃C₆H₄	1-13h	5h	81
9	4-PhC₆H₄	1-13i	5i	82
10	1-C₁₀H₇	1-13j	5j	73
11	2-C₁₀H₇	1-13k	5k	84
12	4-CH₃COC₆H₄	1-13l	5l	68
13	4-CH₃O₂CC₆H₄	1-13m	5m	78
14	4-(CH₃)₃CC₆H₄	1-13n	5n	90
15	4-CNC₆H₄	1-13o	5o	65
16	2-CH₃OC₆H₄	1-13p	5p	88
17	2-CH₃C₆H₄	1-13q	5q	81
18	2,4-(CH₃)₂C₆H₄	1-13r	5r	79
19	3,5-(CH₃)₂C₆H₄	1-13s	5s	85

Entry	Ar	Olefin acid	Lactone	Yield/%
1	C₆H₅	1-13a	5a	80
2	2-ClC₆H₄	1-13b	5b	91
3	3-ClC₆H₄	1-13c	5c	84
4	4-ClC₆H₄	1-13d	5d	69
5	4-CH₃OC₆H₄	1-13e	5e	61
6	4-CH₃C₆H₄	1-13f	5f	75
7	4-FC₆H₄	1-13g	5g	70
8	4-CF₃C₆H₄	1-13h	5h	81
9	4-PhC₆H₄	1-13i	5i	82
10	1-C₁₀H₇	1-13j	5j	73
11	2-C₁₀H₇	1-13k	5k	84
12	4-CH₃COC₆H₄	1-13l	5l	68
13	4-CH₃O₂CC₆H₄	1-13m	5m	78
14	4-(CH₃)₃CC₆H₄	1-13n	5n	90
15	4-CNC₆H₄	1-13o	5o	65
16	2-CH₃OC₆H₄	1-13p	5p	88
17	2-CH₃C₆H₄	1-13q	5q	81
18	2,4-(CH₃)₂C₆H₄	1-13r	5r	79
19	3,5-(CH₃)₂C₆H₄	1-13s	5s	85

Compd.	R. solani	A. solani	S. sclerotiorum	B. cinerea	F. graminearum	P. capsici
5a	10.7	3.7	5.1	0.5	19.4	18.6
R-5a	4.6	2.4	2.8	0.2	13.5	12.0
S-5a	15.5	9.8	10.4	1.4	26.2	25.7
5d	—^a	—	12.3	—	—	—
5i	35.9	—	37.5	11.3	—	35.0
R-5i	12.6	—	13.3	9.7	—	17.9
S-5i	62.8	—	68.6	24.5	—	65.3
5j	—	—	12.8	—	—	—
5k	104.0	—	11.6	23.7	—	40.0
R-5k	64.5	—	4.8	8.6	—	22.7
S-5k	150.8	—	24.4	35.8	—	68.2
5n	54.1	—	15.2	—	—	57.6
R-5n	38.2	—	8.3	—	—	22.1
S-5n	84.5	—	30.8	—	—	88.6
Carbendazim	0.05	0.05	7.9	528.2	0.07	77.8

Compd.	R. solani	A. solani	S. sclerotiorum	B. cinerea	F. graminearum	P. capsici
5a	10.7	3.7	5.1	0.5	19.4	18.6
R-5a	4.6	2.4	2.8	0.2	13.5	12.0
S-5a	15.5	9.8	10.4	1.4	26.2	25.7
5d	—^a	—	12.3	—	—	—
5i	35.9	—	37.5	11.3	—	35.0
R-5i	12.6	—	13.3	9.7	—	17.9
S-5i	62.8	—	68.6	24.5	—	65.3
5j	—	—	12.8	—	—	—
5k	104.0	—	11.6	23.7	—	40.0
R-5k	64.5	—	4.8	8.6	—	22.7
S-5k	150.8	—	24.4	35.8	—	68.2
5n	54.1	—	15.2	—	—	57.6
R-5n	38.2	—	8.3	—	—	22.1
S-5n	84.5	—	30.8	—	—	88.6
Carbendazim	0.05	0.05	7.9	528.2	0.07	77.8

3-芳基-7-甲基-7-羟基-2-辛烯-6-内酯类化合物的合成及杀菌活性