大叶藤黄醇的全合成研究
收稿日期: 2021-06-03
修回日期: 2021-07-08
网络出版日期: 2021-08-10
基金资助
国家自然科学基金(81973438)
Studies toward the Total Synthesis of Xanthochymol
Received date: 2021-06-03
Revised date: 2021-07-08
Online published: 2021-08-10
Supported by
National Natural Science Foundation of China(81973438)
多环多异戊烯基间苯三酚(PPAPs)类天然产物大叶藤黄醇(xanthochymol)具有良好的抗癌和抗菌活性, 目前没有任何关于其全合成的研究报道. 本研究以3,3-二甲基戊二酸为起始原料, 通过一系列步骤制备线性链状底物, 再应用串联Dieckmann缩合反应构建双环[3.3.1]壬烷-2,4,9-三酮核心骨架. 此方法成功地以11步反应实现了消旋体大叶藤黄醇的全合成, 以10%的总收率得到了目标产物. 通过本研究得到大叶藤黄醇侧链的一对非对映异构体, 在1H NMR、13C NMR谱图上明确了它们之间的区别, 也对未来分离鉴定和区分其侧链结构异构体提供了参考数据.
关键词： 多环多异戊烯基间苯三酚(PPAPs); 双环[3.3.1]壬烷; Dieckmann缩合; 串联反应
王学颖 , 盘伊琳 , 郑昌武 , 徐宏喜 . 大叶藤黄醇的全合成研究[J]. 有机化学, 2021 , 41(11) : 4421 -4427 . DOI: 10.6023/cjoc202106009
Xanthochymol, a polycyclic polyprenylated acylphloroglucinol (PPAP) natural compound, has demonstrated good anticancer and antimicrobial properties. However, no related studies on the synthesis of xanthochymol have been reported hitherto. In this study, 3,3-dimethylglutaric acid was used as the starting material to synthesize a key linear precursor via several steps, followed by a domino Dieckmann condensation reaction to construct the bicyclo[3.3.1]nonane-2,4,9-trione core skeleton. With that, the total synthesis of (±)-xanthochymol in 11 steps with a total yield of 10% has been first accomplished. By obtaining the side chain diastereomers of xanthochymol through this study, we have clarified the difference between them on the 1H NMR and 13C NMR spectra while at the same time provided references for future isolation, identification, and discrimination of xanthochymol from its side chain structural isomers.
| [1] | Ciochina, R.; Grossman, R. B. Chem. Rev. 2006, 106, 3963. |
| [2] | Yang, X. W.; Grossman, R. B.; Xu, G. Chem. Rev. 2018, 118, 3508. |
| [3] | Wu, S. B.; Long, C.; Kennelly, E. J. Nat. Prod. Rep. 2014, 31, 1158. |
| [4] | Bridi, H.; Meirelles, G. C.; von Poser, G. L. Phytochemistry 2018, 155, 203. |
| [5] | Gurevich, A. I.; Dobrynin, V. N.; Kolosov, M. N.; Popravko, S. A.; Riabova, I. D. Antibiotiki 1971, 16, 510. |
| [6] | Grossman, R. B. Table of Naturally Occurring PPAPs. |
| [7] | Nicolaou, K. C.; Pfefferkorn, J. A.; Kim, S.; Wei, H. X. J. Am. Chem. Soc. 1999, 121, 4724. |
| [8] | Spessard, S. J.; Stoltz, B. M. Org. Lett. 2002, 4, 1943. |
| [9] | Usuda, H.; Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2002, 43, 3621. |
| [10] | Kraus, G. A.; Nguyen, T. H.; Jeon, I. Tetrahedron Lett. 2003, 44, 659. |
| [11] | Mehta, G.; Bera, M. K. Tetrahedron Lett. 2004, 45, 1113. |
| [12] | Kuramochi, A.; Usuda, H.; Yamatsugu, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 14200. |
| [13] | Karanjgoakar, C.; Rao, A. R.; Venkataraman, K.; Yemul, S.; Palmer, K. Tetrahedron Lett. 1973, 14, 4977. |
| [14] | Protiva, P.; Hopkins, M. E.; Baggett, S.; Yang, H.; Lipkin, M.; Holt, P. R.; Kennelly, E. J.; Bernard, W. I. Int. J. Cancer 2008, 123, 687. |
| [15] | Saxe Einbond, L.; Mighty, J.; Kashiwazaki, R.; Figueroa, M.; Jalees, F.; Munoz Acuna, U.; LeGendre, O.; A. Foster, D.; J. Kennelly, E. Anticancer Agents Med. Chem. 2013, 13, 1540. |
| [16] | Matsumoto, K.; Akao, Y.; Kobayashi, E.; Ito, T.; Ohguchi, K.; Tanaka, T.; Iinuma, M.; Nozawa, Y. Biol. Pharm. Bull. 2003, 26, 569. |
| [17] | Iinuma, M.; Tosa, H.; Tanaka, T.; Kanamaru, S.; Asai, F.; Kobayashi, Y.; Miyauchi, K.; Shimano, R. Biol. Pharm. Bull. 1996, 19, 311. |
| [18] | Gustafson, K. R.; Blunt, J. W.; Munro, M. H. G.; Fuller, R. W.; McKee, T. C.; Cardellina, J. H.; McMahon, J. B.; Cragg, G. M.; Boyd, M. R. Tetrahedron 1992, 48, 10093. |
| [19] | Baggett, S.; Mazzola, E. P.; Kennelly, E. J. Studies in Natural Products Chemistry, Vol. 32, Ed.: Atta-ur-Rahman, Elsevier, Amsterdam, 2005, p. 721. |
| [20] | Wang, L.; Sun, L.; Wang, X.; Wu, R.; Zhou, H.; Zheng, C.; Xu, H. Org. Lett. 2019, 21, 8075. |
| [21] | Wang, X.; Phang, Y.; Feng, J.; Liu, S.; Zhang, H.; Fu, W.; Zhou, H.; Xu, G.; Xu, H.; Zheng, C. Org. Lett. 2021, 23, 4203. |
| [22] | Pepper, H. P.; Tulip, S. J.; Nakano, Y.; George, J. H. J. Org. Chem. 2014, 79, 2564. |
| [23] | Wang, L.; Wang, X.; Zhang, G.; Fu, W.; Zhang, H.; Zhou, H.; Xu, H.; Zheng, C. Org. Chem. Front. 2021, 8, 2525. |
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