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

doi:10.6023/cjoc202101049

摘要/Abstract

为了优化3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯的化学结构, 通过环氧化-内酯化和Sharpless不对称双羟基化反应作为关键步骤, 分别以61%~91%的收率实现了消旋及光活性3-芳基-7-甲基-7-羟基-2-辛烯-6-内酯类化合物的合成, 其结构经过IR, ¹H NMR, ¹³C NMR和HR-ESI-MS的表征. 对它们的杀菌活性进行了评价, 结果表明(R)-3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯(5a)活性最好的化合物, 对6种植物病原菌的EC₅₀值在0.2~13.5 µg/mL范围, 优于其( S)-异构体及消旋体混合物. 它可以作为先导结构进行进一步结构优化. 扫描电镜和透射电镜观测的结果显示, 化合物(S)-5a,5d和5j对油菜菌核菌菌丝细胞的结构和功能有显著影响.

关键词: 3-芳基-7-甲基-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

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

引用此文

王卫伟, 赵宇, 刘鑫磊, 蒋家珍, 王明安. 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[J]. 有机化学, 2021, 41(6): 2343-2353.

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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[1]	Gabriela, L.; Gallardo, N. I. P.; Cabrera, G. M. Phytochem. Lett. 2008, 1,155. doi: 10.1016/j.phytol.2008.07.008
[2]	Yang, Y.; Jiang, J. Z.; Qimei, L. B.; Yan, X. J.; Zhao, J. X.; Yuan, H. Z.; Qin, Z. H.; Wang, M. A. Molecules 2010, 15,7075. doi: 10.3390/molecules15107075 pmid: 20944522
[3]	Schulz, S.; Hotling, S. Nat. Prod. Rep. 2015, 32,1042. doi: 10.1039/C5NP00006H
[4]	Davies-Coleman, M. T.; Rivett, D. E. A. Prog. Chem. Org. Nat. Prod. 1989, 55,1.
[5]	Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A. Prog. Chem. Org. Nat. Prod. 1998, 75,182.
[6]	Pereda-Miranda, R.; Fragoso-Serrano, M.; Cerda-Garcia-Rojas, C. M. Tetrahedron 2001, 57,47. doi: 10.1016/S0040-4020(00)00987-X
[7]	Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. 1985, 24,94. doi: 10.1002/(ISSN)1521-3773
[8]	Marco, J. A.; Carda, M.; Murga, J.; Falomir, E. Tetrahedron 2007, 63,2929. doi: 10.1016/j.tet.2006.12.047
[9]	Boucard, V.; Broustal, G.; Campagne, J. M. Eur. J. Org. Chem. 2007,225.
[10]	Gerard, R. Tetrahedron 1995, 51,2777. doi: 10.1016/0040-4020(94)01064-7
[11]	Helena, M. C.; Fernanda, I. B.; Myrian, K. S.; Luiz, S. L. J. Quim. Nova 2008, 31,885. doi: 10.1590/S0100-40422008000400029
[12]	Helena, M. C.; Fernanda, I. B.; Luiz, S. L. J. Synthesis 2007,3261.
[13]	Shiina, I. Chem. Rev. 2007, 107,239. pmid: 17212476
[14]	Chang, H.-T.; Jayanth, T. T.; Wang, C.-C.; Cheng, C.-H. J. Am. Chem. Soc. 2007, 129,12032. doi: 10.1021/ja073604c
[15]	Ebine, M.; Suga, Y.; Fuwa, H.; Sasaki, M. Org. Biomol. Chem. 2010, 8,39. doi: 10.1039/B919673K
[16]	Emily, B. P.; Tendai, G.; Sonbinh, T. N. Org. Lett. 2008, 10,5613. doi: 10.1021/ol8022227
[17]	van, As, B. A. C.; Chan, D.; Kivit, P. J. J.; Palmans, A. R. A.; Meijer, E. W. Tetrahedron: Asymmetry 2007, 18,787. doi: 10.1016/j.tetasy.2007.03.016
[18]	Maxime, A. S.; Huub, K.; Anthony, L. S. Acta Cryst. 2008,E64, o607.
[19]	Fukuzawa, A.; Masamune, T. Tetrahedron Lett. 1981, 22, 4081. doi: 10.1016/S0040-4039(01)82070-0
[20]	Cremer, D. J.; Pople, A. J. Am. Chem. Soc. 1975, 97,1354. doi: 10.1021/ja00839a011
[21]	Wandjia, J.; Wansi, J. D.; Fuendjiep, V.; Dagne, E.; Mulholland, D. A.; Tillequin, F.; Fomum, Z. T.; Sondengam, B. L.; Nkeh, B. C.; Njamen, D. Phytochemistry 2000, 54,811. pmid: 11014271
[22]	Nkeh, B. C.; Njamen, D.; Wandjia, J.; Fomum, Z. T.; Dongmo, A.; Nguelefack, T. B.; Wansi, J. D.; Kamanyi, A. Pharm. Biol. 2003, 41,26. doi: 10.1076/phbi.41.1.26.14704
[23]	Jhulki, S.; Seth, S.; Mondal, M.; Moorthy, J. N. Tetrahedron 2014, 70,2286. doi: 10.1016/j.tet.2014.01.034
[24]	Kadnikov, D. V.; Larock, R. C. Mendeleev Commun. 2007, 17,74. doi: 10.1016/j.mencom.2007.03.006
[25]	Cheng, Y. A.; Chen, T.; Tan, C. K.; Heng, J. J.; Yeung, Y. Y. J. Am. Chem. Soc. 2012, 134,16492. doi: 10.1021/ja307210n pmid: 22998611
[26]	Wang, L.; Ren, Z.-L.; Ding, M.-W. J. Org. Chem. 2015, 80,641. doi: 10.1021/jo502275f
[27]	Arcadi, A.; Fabrizi, G.; Goggiamani, A.; Marinelli, F. J. Org. Chem. 2015, 80,6986. doi: 10.1021/acs.joc.5b00663
[28]	Matsuda, T.; Shigeno, M.; Murakami, M. Org. Lett. 2008, 10,5219. doi: 10.1021/ol802218a
[29]	Zarrabi, S.; Mahmoodi, N. O.; Tabatabaeian, K.; Zanjanchi, M. A. Chin. Chem. Lett. 2009, 20,1400. doi: 10.1016/j.cclet.2009.07.007
[30]	Dong, H. B.; Yang, M. Y.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2013, 15,880. doi: 10.1080/10286020.2013.803474
[31]	Dong, H. B.; Yang, M. Y.; Tang, B.; Wang, M. A. Chin. J. Org. Chem. 2014, 34,2350(in Chinese). doi: 10.6023/cjoc201406005
	( 董宏波, 杨明艳, 汤博, 王明安, 有机化学, 2014, 34,2350.) doi: 10.6023/cjoc201406005
[32]	Zhao, J.; Dong, H. B.; Yang, M. Y.; Du, J.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2014, 16,312. doi: 10.1080/10286020.2013.879121 pmid: 24456253
[33]	Dong, H. B.; Wang, W. W.; Zhao, Y.; Liu, X. L.; Wang, M. A. Chin. J. Org. Chem. 2021, 41,1646(in Chinese). doi: 10.6023/cjoc202010011
	( 董宏波, 王卫伟, 赵宇, 刘鑫磊, 王明安, 有机化学, 2021, 41,1646.) doi: 10.6023/cjoc202010011
[34]	Yonova, I. M.; Johnson, A. G.; Osborne, C. A.; Moore, C. E.; Morrissette, N. S.; Jorvo, E. R. Angew. Chem., Int. Ed. 2014, 53,2422. doi: 10.1002/anie.201308666
[35]	Touchard, F. P. Tetrahedron Lett. 2004, 45,5519. doi: 10.1016/j.tetlet.2004.05.026
[36]	Wang, W. W.; Zhao, Y.; Liu, X. L.; Geng, R.; Wang, M. A. Chin. J. Org. Chem. 2019, 39,1129(in Chinese).
	( 王卫伟, 赵宇, 刘鑫磊, 耿瑞, 王明安, 有机化学, 2019, 39,1129.) doi: 10.6023/cjoc201809018
[37]	Tang, B.; Guan, A. Y.; Zhao, Y.; Jiang, J. Z.; Wang, M. A.; Zhou, L. G. Chin. J. Chem. 2017, 35,1133. doi: 10.1002/cjoc.v35.7
[38]	Zhao, Y.; Tang, B.; Guan, A. Y.; Wang, W. W.; Zhang, Z. H.; Wang, M. A. Synthesis 2017, 49,4663. doi: 10.1055/s-0036-1588463
[39]	Geng, R.; Zhao, Y.; Li, Y. H.; Liu, X. L.; Wang, M. A. Chin. J. Org. Chem. 2019, 39,3574(in Chinese). doi: 10.6023/cjoc201906017
	( 耿瑞, 赵宇, 李益豪, 刘鑫磊, 王明安, 有机化学, 2019, 39,3574.) doi: 10.6023/cjoc201906017
[40]	Schwartz, B. D.; Tilly, D. P.; Heim, R.; Wiedemann, S.; Williams, C. M.; Bernhardt, P. V. Eur. J. Org. Chem. 2006,3181.
[41]	Anastasia, L.; Dumond, Y. R.; Negishi, E. Eur. J. Org. Chem. 2001,3039.
[42]	Derrick, L. J.; Clive, V. F.; Pierre, L. B. J. Org. Chem. 1982, 47,2572. doi: 10.1021/jo00134a013

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