Palmarumycin B6类似物的合成及杀蚊活性

doi:10.6023/cjoc202109018

有机化学 ›› 2022, Vol. 42 ›› Issue (2): 519-525.DOI: 10.6023/cjoc202109018 上一篇下一篇

研究论文

Palmarumycin B₆类似物的合成及杀蚊活性

刘鑫磊, 许磊川, 安鑫鲲, 蒋家珍, 王明安^*()

中国农业大学应用化学系农药创新研究中心北京 100193

收稿日期:2021-09-13 修回日期:2021-09-29 发布日期:2022-02-24
通讯作者: 王明安
基金资助:
国家自然科学基金(21772229)

Synthesis and Larvicidal Activity of Palmarumycin B₆ Analogues

Xinlei Liu, Leichuan Xu, Xinkun An, Jiazhen Jiang, Ming'an Wang()

Innovation Center of Pesticide Research, Department of Applied Chemistry, China Agricultural University, Beijing 100193

Received:2021-09-13 Revised:2021-09-29 Published:2022-02-24
Contact: Ming'an Wang
Supported by:
National Natural Science Foundation of China(21772229)

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摘要/Abstract

为了提高天然产物Palmarumycin B₆的生物活性, 通过取代四氢萘酮烯醇醚和1,8-二羟基萘的缩酮化反应以及吡啶重铬酸盐和过氧叔丁醇参与的苄位氧化反应作为关键步骤完成了多个Palmarumycin B₆ A环含氯和含氟类似物的合成, 它们的结构经过¹H NMR, ¹³C NMR和HR-ESI-MS的表征. 对它们的杀蚊活性进行了评价, 结果表明6-氯-5-羟基- 2,3-二氢-4H-螺[萘-1,2'-萘[1,8-de][1,3]-二噁烷]-4-酮(4m)和6-氟-5-羟基-2,3-二氢-4H-螺[萘-1,2'-萘[1,8-de][1,3]-二噁烷]-4-酮(4i)是活性最好的化合物,对白纹伊蚊的LC₅₀值为11.51和23.25 µg/mL,它们可以作为先导结构进行进一步结构优化. 在6位的卤素原子、5-羟基和4-羰基对该类Palmarumycin B₆类似物的杀蚊活性起到了关键作用.

关键词: 螺二萘, Palmarumycin B₆, 缩酮化反应, 苄位氧化反应, 杀蚊活性

In order to improve the biological activity of naturally occurring Palmarumycin B₆, the synthesis of Palmarumycin B₆ chlorine- and fluorine-containing analogues at A ring has been achieved via ketalization of substituted 1-tetralone enol ether with 1,8-dihydroxynaphthalene and the benzyl oxidation involving pyridinium dichromate and t-BuOOH as the key steps. Their structures were fully characterized by ¹H NMR, ¹³C NMR, and HR-ESI-MS data. Their larvicidal activities were evaluated and showed that 6-chloro-5-hydroxy-2,3-dihydro-4H-spiro[naphthalene-1,2'-naphtho[1,8-de]-[1,3]dioxin]-4-one (4m) and 6-fluoro-5-hydroxy-2,3-dihydro-4H-spiro[naphthalene-1,2'-naphtho[1,8-de][1,3]dioxin]-4-one (4i) were the most active compounds with the LC₅₀values of 11.51 and 23.25 µg/mL against Aedes albopictus, and they would be the potential lead structure to be optimized. The halogen atoms at C-6, 5-hydroxy and 4-carbonyl play a critical role for the larvicidal activities of this type of Palmarumycin B₆ analogues.

Key words: spirobisnaphthalene, Palmarumycin B6, ketalization, benzyl oxidation, larvicidal activity

引用此文

刘鑫磊, 许磊川, 安鑫鲲, 蒋家珍, 王明安. Palmarumycin B₆类似物的合成及杀蚊活性[J]. 有机化学, 2022, 42(2): 519-525.

Xinlei Liu, Leichuan Xu, Xinkun An, Jiazhen Jiang, Ming'an Wang. Synthesis and Larvicidal Activity of Palmarumycin B₆ Analogues[J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 519-525.

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图/表 5

Figure 1. Representing naturally occurring spirobisnaphthalene synthesized in our laboratory[22⇓-24]

Scheme 1. Design strategy of Palmarumycin B6 chlorine- and fluorine-containing analogues

Scheme 3. Synthesis exploration of Palmarumycins B6 6,8- dihalogen analogues

Scheme 4. Structures of Palmarumycins B6, its regioisomer and their synthetic intermediates[23]

Compd.	LC₅₀	Compd.	LC₅₀	Compd.	LC₅₀
3a	>200	4a	>200	4j	97.08
3b	>200	4b	187.24	4k	67.36
3c	>200	4c	>200	4l	130.27
3d	>200	4d	>200	4m	11.51^[23]
3e	>200	4e	155.49	4n	80.11^[23]
3f	143.28	4f	127.61	Rotenone	3.75
3g	>200	4g	170.53	Juglone	6.19
3h	122.17	4h	82.31
3i	>200	4i	23.25

Table 1. LC50 (µg/mL) values for larvicidal activity against A. albopictus of the title compounds 3 and 4

参考文献 39

[1]	Miyashita, K.; Imanishi, T. Chem. Rev. 2005, 105, 4515. pmid: 16351052
[2]	Zhou, L.; Zhao, J.; Shao, T.; Cai, X.; Peng, Y. Mini-Rev. Med. Chem. 2010, 10, 977.
[3]	Cai, Y. S.; Guo, Y. W.; Krohn, K. Nat. Prod. Rep. 2010, 27, 1840. doi: 10.1039/c0np00031k
[4]	Liu, X.; Zhao, Y.; Wang, W.; Wang, M.; Zhou, L. Chin. J. Org. Chem. 2017, 37, 2883. (in Chinese) doi: 10.6023/cjoc201705020
	( 刘鑫磊, 赵宇, 王卫伟, 王明安, 周立刚, 有机化学, 2017, 37, 2883.) doi: 10.6023/cjoc201705020
[5]	Aslan, A.; Altun, S.; Ahmed, I.; Florke, U.; Schulz, B.; Krohn, K. Eur. J. Org. Chem. 2011, 1176.
[6]	Tsukamoto, H.; Hanada, S.; Kumasaka, K.; Kagaya, N.; Izumikawa, M.; Shinya, K.; Doi, T. Org. Lett. 2016, 18, 4848. pmid: 27648608
[7]	Ando, Y.; Hanaki, A.; Sasaki, R.; Ohmori, K.; Suzuki, K. Angew. Chem., nt. Ed. 2017, 56, 11460. doi: 10.1002/anie.v56.38
[8]	Chinta, B. S.; Baire, B. Eur. J. Org. Chem. 2017, 3457.
[9]	Tsukamoto, H.; Nomura, Y.; Fujiwara, K.; Hanada, S.; Doi, T. Org. Lett. 2018, 20, 3140. doi: 10.1021/acs.orglett.8b01259 pmid: 29737863
[10]	Tsukamoto, H.; Hanada, S.; Nomura, Y.; Doi, T. J. Org. Chem. 2018, 83, 9430. doi: 10.1021/acs.joc.8b01075 pmid: 29895147
[11]	Yue, Z.; Lam, H. C.; Chen, K.; Siridechakorn, I.; Liu, Y.; Pudhom, K.; Lei, X. Angew. Chem., nt. Ed. 2019, 59, 4115. doi: 10.1002/anie.v59.10
[12]	Ando, Y.; Tanaka, D.; Sasaki, R.; Ohmori, K.; Suzuki, K. Angew. Chem., nt. Ed. 2019, 58, 12507. doi: 10.1002/anie.v58.36
[13]	Siridechakorn, I.; Yue, Z.; Mittraphab, Y.; Lei, X.; Pudhom, K. Bioorg. Med. Chem. 2017, 25, 2878. doi: 10.1016/j.bmc.2017.02.054
[14]	Chen, S.; Chen, D.; Cai, R.; Cui, H.; Long, Y.; Lu, Y.; Li, C.; She, Z. J. Nat. Prod. 2016, 79, 2397. doi: 10.1021/acs.jnatprod.6b00639
[15]	Li, J.; Ding, R.; Gao, H.; Guo, L.; Yao, X.; Zhang, Y.; Tang, J. RSC Adv. 2019, 9, 39082. doi: 10.1039/C9RA07917C
[16]	Shan, T.; Tian, J.; Wang, X.; Mou, Y.; Mao, Z.; Lai, D.; Dai, J.; Peng, Y.; Zhou, L.; Wang, M. J. Nat. Prod. 2014, 77, 2151. doi: 10.1021/np400988a
[17]	Tian, J.; Liu, X.; Liu, Z.; Lai, D.; Zhou, L. Pest Manage. Sci. 2016, 72, 961. doi: 10.1002/ps.4075
[18]	Schmidt, B.; Petersen, M. H.; Braun, D. J. Org. Chem. 2018, 83, 1627. doi: 10.1021/acs.joc.7b02944 pmid: 29294276
[19]	Franca, R. F. O.; Neves, M. H. L.; Ayres, C. F. J.; Melo-Neto, O. P.; Filho, S. P. B. Plos Neglected Trop. Dis. 2016, 10, e0004760. doi: 10.1371/journal.pntd.0004760
[20]	Schechtman, H.; Souza, M. O. Plos One 2015, 10, e0123961 doi: 10.1371/journal.pone.0123961
[21]	Rodriguez, M. M.; Hurtado, D.; Severson, D. W.; Bisset, J. A. J. Med. Entomol. 2014, 51, 1213. doi: 10.1603/ME13237
[22]	Wang, R.; Liu, G.; Yang, M.; Wang, M.; Zhou, L. Molecules 2016, 21, 600. doi: 10.3390/molecules21050600
[23]	Liu, X.; Wang, W.; Zhao, Y.; Lai, D.; Zhou, L.; Liu, Z.; Wang, M. J. Nat. Prod., 2018, 81, 1803. doi: 10.1021/acs.jnatprod.8b00258
[24]	Liu, X.; Li, S.; Wei, X.; Zhao, Y.; Lai, D.; Zhou, L.; Wang, M. RSC Adv. 2020, 10, 1588. doi: 10.1039/C9RA10316C
[25]	Kim, M.-G.; Jeon, J.-H.; Lee, H.-S. J. Agric. Food Chem. 2013, 61, 10741. doi: 10.1021/jf403679h
[26]	Ribeiro, K. A. L.; de Carvalho, C. M.; Molina, M. T.; Lima, E. P.; López-Montero, E.; Reys, J. R. M. Acta Trop. 2009, 111, 44. doi: 10.1016/j.actatropica.2009.02.008 pmid: 19426662
[27]	Jewess, P. J.; Chamberlain, K.; Boogaard, A. B.; Devonshire, A. L.; Khambay, B. P. S. Pest Manage. Sci. 2002, 58, 243. doi: 10.1002/(ISSN)1526-4998
[28]	Khambay, B. P.; Batty, D.; Cahill, M.; Denholm, I.; Mead-Briggs, M.; Vinall, S.; Niemeyer, H. M.; Simmonds, M. S. J. Agric. Food Chem. 1999, 47, 770. doi: 10.1021/jf980769j
[29]	Baumli, S.; Endicott, J. A.; Johnson L. N. Chem. Biol. 2010, 17, 931. doi: 10.1016/j.chembiol.2010.07.012
[30]	Ren, C.; Ding, X.; Roy, A.; Shen, J.; Zhou, S.; Chen, F.; Li, S. F. Y.; Ren, H.; Yang, Y. Y.; Zeng, H. Chem. Sci., 2018, 9, 4044. doi: 10.1039/C8SC00602D
[31]	O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308. doi: 10.1039/B711844A
[32]	Callejo, R.; Corr, M. J.; Yang, M.; Wang, M.; Cordes, D. B.; Slawin, A. M. Z.; O’Hagan, D. Chem.-Eur. J., 2016, 22, 8137. doi: 10.1002/chem.201600519
[33]	Barrett, A. G. M.; Hamprecht, D.; Meyer, T. Chem. Commun. 1998, 8, 809.
[34]	Ragot, J.; Steeneck, C.; Alcaraz, M.; Taylor, R. J. Chem. Soc., erkin Trans. 1 1999, 1073.
[35]	Yoshimura, H.; Nagai, M.; Hibi, S.; Kikuchi, K.; Abe, S.; Hida, T.; Higashi, S.; Hishinuma, I.; Yamanaka, T. J. Med. Chem. 1995, 38, 3163. pmid: 7636879
[36]	Lee, W.-G.; Chan, A. H.; Spasov, K. A.; Anderson, K. S.; Jorgensen, W. L. ACS Med. Chem. Lett. 2016, 7, 1156. doi: 10.1021/acsmedchemlett.6b00390
[37]	Weinstock, J.; Gaitanopoulos, D.; Oh, H. J.; Pfeiffer, F. R.; Karash, C. B.; Venslavsky, J. W.; Sarau, H. M.; Flaim, K. E.; Hieble, J. P.; Kaiser, C. J. Med. Chem. 1986, 29, 1615. pmid: 2875183
[38]	Owton, W. M. J. Chem. Soc., erkin Trans. 1 1994, 2131.
[39]	Koerner, S. K.; Hanai, J. I.; Bai, S.; Jernigan, F. E.; Oki, M.; Komaba, C.; Shuto, E.; Sukhatme, V. P.; Sun, L. Eur. J. Med. Chem. 2017, 126, 920. doi: S0223-5234(16)31024-8 pmid: 27997879

Palmarumycin B₆类似物的合成及杀蚊活性

Synthesis and Larvicidal Activity of Palmarumycin B₆ Analogues

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