3,7-二甲基-7-羟基-2-辛烯-6-内酯类似物的合成及杀菌活性

doi:10.6023/cjoc202010011

摘要/Abstract

以环氧化-内酯化和Sharpless不对称双羟基化反应作为关键步骤, 以55%~90%的总收率实现了消旋及光活性3,7-二甲基-7-羟基-2-辛烯-6-内酯类似物的合成. 它们的结构经过¹H NMR, ¹³C NMR, HR-ESI-MS和X射线衍射的表征. 对它们的杀菌活性进行了评价, 结果表明活性最好的化合物3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯(4)和3-(呋喃-2-基)-7-甲基-7-羟基-2-辛烯-6-内酯(5)对6种植物病原菌的EC₅₀值为0.5~20.0 μg/mL, 可以作为先导结构进行进一步结构优化.

关键词: 3,7-二甲基-7-羟基-2-辛烯-6-内酯, 环氧化-内酯化反应, 不对称双羟基化反应, 杀菌活性

The synthesis of racemic and optical 3,7-dimethyl-7-hydroxy-2-octen-6-olide analogues has been achieved via epoxidation-lactonization procedure and Sharpless asymmetric dihydroxylation as the key steps in 55%~90% overall yields, respectively. Their structures were fully characterized by ¹H NMR, ¹³C NMR, HRMS data, and X-ray diffraction analysis. Their antifungal activities were evaluated, and showed that the EC₅₀values of the most active compounds 3-phenyl-7- methyl-7-hydroxy-2-octen-6-olide (4) and 3-(furan-2-yl)-7-methyl-7-hydroxy-2-octen-6-olide (5) were in the range of 0.5~20.0 μg/mL against the tested six phytopathgens, and they were the lead structures to be optimized.

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

引用此文

董宏波, 王卫伟, 赵宇, 刘鑫磊, 王明安. 3,7-二甲基-7-羟基-2-辛烯-6-内酯类似物的合成及杀菌活性[J]. 有机化学, 2021, 41(4): 1646-1657.

Hongbo Dong, Weiwei Wang, Yu Zhao, Xinlei Liu, Ming'an Wang. Synthesis and Antifungal Activity of 3,7-Dimethyl-7-hydroxy-2-octen-6-olide Analogues[J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1646-1657.

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Entry	R	Olefin acid	Lactone	Yield^a/%	Entry	R	Olefin acid	Lactone	Yield^a/%
1	CH₃	1b	1	65	9	8-Cl	9a	9	70
2	CF₃	2b	2	90	10	7-OCH₃	10a	10	74
3	OCH₃	3b	3	77	11	6-OCH₃	11a	11	80
4	C₆H₅	4b	4	62	12	6-Cl	12a	12	78
5	2-C₄H₃O	5b	5	60	13	7,9-(OCH₃)₂	13a	13	85
6	H	6a	6	86	14				72
7	8-CH₃	7a	7	76	15				80
8	8-F	8a	8	75	16				73

Entry	R	Olefin acid	Lactone	Yield^a/%	Entry	R	Olefin acid	Lactone	Yield^a/%
1	CH₃	1b	1	65	9	8-Cl	9a	9	70
2	CF₃	2b	2	90	10	7-OCH₃	10a	10	74
3	OCH₃	3b	3	77	11	6-OCH₃	11a	11	80
4	C₆H₅	4b	4	62	12	6-Cl	12a	12	78
5	2-C₄H₃O	5b	5	60	13	7,9-(OCH₃)₂	13a	13	85
6	H	6a	6	86	14				72
7	8-CH₃	7a	7	76	15				80
8	8-F	8a	8	75	16				73

Compd.	R. solani	A. solani	S. sclerotiorum	B. cinerea	F. graminearum	P. capsici
1	65.7	42.2	—^a	—	—	—
R-1	56.5	44.9	—	—	—	—
S-1	231.6	52.0	—	—	—	—
2	—	—	—	—	—	—
3	75.6	23.5	—	—	—	—
R-3	87.1	32.3	—	—	—	—
S-3	73.0	40.5	—	—	—	—
4	10.7	3.7	5.1	0.5	19.4	18.6
5	2.8	4.6	9.8	-	10.7	5.1
6	—	115.1	—	—	—	—
R-6	—	27.4	—	—	—	—
S-6	—	18.4	—	—	—	—
7	48.9	—	—	—	323.7	—
8	134.2	8.1	186.8	—	132.9	—
9	—	—	—	—	—	—
10	—	—	—	—	—	—
11	—	—	—	—	—	—
12	—	—	—	—	—	—
13	41.4	6.6	—	—	—	—
14	—	—	—	—	—	—
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
1	65.7	42.2	—^a	—	—	—
R-1	56.5	44.9	—	—	—	—
S-1	231.6	52.0	—	—	—	—
2	—	—	—	—	—	—
3	75.6	23.5	—	—	—	—
R-3	87.1	32.3	—	—	—	—
S-3	73.0	40.5	—	—	—	—
4	10.7	3.7	5.1	0.5	19.4	18.6
5	2.8	4.6	9.8	-	10.7	5.1
6	—	115.1	—	—	—	—
R-6	—	27.4	—	—	—	—
S-6	—	18.4	—	—	—	—
7	48.9	—	—	—	323.7	—
8	134.2	8.1	186.8	—	132.9	—
9	—	—	—	—	—	—
10	—	—	—	—	—	—
11	—	—	—	—	—	—
12	—	—	—	—	—	—
13	41.4	6.6	—	—	—	—
14	—	—	—	—	—	—
Carbendazim	0.05	0.05	7.9	528.2	0.07	77.8