Synthesis and Antifungal Activity of 3,7-Dimethyl-7-hydroxy-2-octen-6-olide Analogues

doi:10.6023/cjoc202010011

Abstract

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

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 12

References 50

[1]	Schulz, S.; Hotling, S. Nat. Prod. Rep. 2015, 32,1042.
[2]	Gabriela, L.; Gallardo, N.I. P.; Cabrera, G.M. Phytochem. Lett. 2008, 1,155.
[3]	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.
[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.
[7]	Hoffmann, H.M. R.; Rabe, J. Angew. Chem. Int. Ed. 1985, 24,94.
[8]	Marco, J.A.; Carda, M.; Murga, J.; Falomir, E. Tetrahedron 2007, 63,2929.
[9]	Boucard, V.; Broustal, G.; Campagne, J.M. Eur. J. Org. Chem. 2007,225.
[10]	Gerard, R. Tetrahedron 1995, 51,2777.
[11]	Helena, M.C.; Fernanda, I.B.; Myrian, K.S.; Luiz, S.L. J. Quim. Nova 2008, 31,885.
[12]	Helena, M.C.; Fernanda, I.B.; Luiz, S.L. J. Synthesis 2007,3261.
[13]	Shiina, I. Chem. Rev. 2007, 107,239.
[14]	Chang, H.-T.; Jayanth, T.T.; Wang, C.-C.; Cheng, C.-H. J. Am. Chem. Soc. 2007, 129,12032.
[15]	Ebine, M.; Suga, Y.; Fuwa, H.; Sasaki, M. Org. Biomol. Chem. 2010, 8,39.
[16]	Emily, B.P.; Tendai, G.; Sonbinh, T.N. Org. Lett. 2008, 10,5613.
[17]	van, As, B.A. C.; Chan, D.; Kivit, P.J. J.; Palmans, A.R. A.; Meijer, E.W. Tetrahedron: Asymmetry 2007, 18,787.
[18]	Maxime, A.S.; Huub, K.; Anthony, L.S. Acta Crystallogr. 2008, E64,o607.
[19]	Fukuzawa, A.; Masamune, T. Tetrahedron Lett. 1981, 22,4081.
[20]	Cremer, D.J.; Pople, A. J. Am. Chem. Soc. 1975, 97,1354.
[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.
[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.
[23]	Jhulki, S.; Seth, S.; Mondal, M.; Moorthy, J.N. Tetrahedron 2014, 70,2286.
[24]	Kadnikov, D.V.; Larock, R.C. Mendeleev Commun. 2007, 17,74.
[25]	Cheng, Y.A.; Chen, T.; Tan, C.K.; Heng, J.J.; Yeung, Y.Y. J. Am. Chem. Soc. 2012, 134,16492.
[26]	Wang, L.; Ren, Z.-L.; Ding, M.-W. J. Org. Chem. 2015, 80,641.
[27]	Arcadi, A.; Fabrizi, G.; Goggiamani, A.; Marinelli, F. J. Org. Chem. 2015, 80,6986.
[28]	Matsuda, T.; Shigeno, M.; Murakami, M. Org. Lett. 2008, 10,5219. pmid: 18954068
[29]	Zarrabi, S.; Mahmoodi, N.O.; Tabatabaeian, K.; Zanjanchi, M.A. Chin. Chem. Lett. 2009, 20,1400.
[30]	Dong, H. B.; Yang, M. Y.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2013, 15,880.
[31]	Dong, H. B.; Yang, M. Y.; Tang, B.; Wang, M. A. Chin. J. Org. Chem. 2014, 34,2350. (in Chinese)
	( 董宏波, 杨明艳, 汤博, 王明安, 有机化学, 2014, 34,2350.)
[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.
[33]	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.)
[34]	Srivastava, A.K.; Song, H.; Park, S.B. Synthesis 2011,1708.
[35]	Gesinski, M.R.; Tadpetch, K.; Rychnovsky, S.D. Org. Lett. 2009, 11,5342.
[36]	Matsuda, T.; Shigeno, M.; Murakami, M. Org. Lett. 2008, 10,5219.
[37]	Chang, H.T.; Jeganmohan, M.; Cheng, C.H. Chem. Commun. 2005,4955.
[38]	Roux, M.C.; Paugam, R.; Rousseau, G. J. Org. Chem. 2001, 66,4304.
[39]	Wong, O.A.; Shi, Y. Chem. Rev. 2008, 108,3958.
[40]	Dong, H.B.; Yang, M.Y.; Liu, B.; Wang, M.A. J. Asian Nat. Prod. Res. 2014, 16,847.
[41]	Kolb, H.C.; Van Nieuwenhze, M.S.; Sharpless, K.B. Chem. Rev. 1994, 94,2483.
[42]	Dong, H.B.; Yang, M.Y.; Zhang, X.T.; Wang, M.A. Tetrahedron: Asymmetry 2014, 25,610.
[43]	Jorge, G.-F.; Juan, M.; Miguel, C.; Alberto, M.J. Org. Lett. 2006, 8,2695.
[44]	Narender, T.; Sarkar, S.; Rajendar, K.; Tiwari, S. Org. Lett. 2011, 13,6140.
[45]	Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc. Jpn. 1979, 52,1989.
[46]	Yadav, J.S.; Rajendar, G.; Rao, R.S.; Pabbaraja, S. J. Org. Chem. 2013, 78,8524.
[47]	Ikuko, O.; Takenori, K.; Yoel, K.; Hiroshi, K. J. Am. Chem. Soc. 1991, 113,4092.
[48]	Tang, B.; Guan, A.Y.; Zhao, Y.; Jiang, J.Z.; Wang, M.A.; Zhou, L.G. Chin. J. Chem. 2017, 35,1133.
[49]	Zhao, Y.; Tang, B.; Guan, A.Y.; Wang, W.W.; Zhang, Z.H.; Wang, M.A. Synthesis 2017, 49,4663.
[50]	Geng, R.; Zhao, Y.; Li, Y.H.; Liu, X.L.; Wang, M.A. Chin. J. Org. Chem. 2019, 39,3574. (in Chinese)
	( 耿瑞, 赵宇, 李益豪, 刘鑫磊, 王明安, 有机化学, 2019, 39,3574.)

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

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