Studies on the Chemical Synthesis of Natural Drugs Berberine

doi:10.6023/cjoc202012053

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (6): 2217-2227.DOI: 10.6023/cjoc202012053 Previous Articles Next Articles

REVIEWS

天然药物小檗碱的化学合成研究进展

严锡飞^a, 郑剑峰^a^,^*(), 李卫东^a^,^b^,^*()

a 西南交通大学生命科学与工程学院四川省天然药物仿生合成工程研究中心成都 610031
b 伊犁师范大学新疆天然产物化学与应用重点实验室新疆伊宁 835000

收稿日期:2020-12-31 修回日期:2021-01-26 发布日期:2021-02-26
通讯作者: 郑剑峰, 李卫东
基金资助:
国家自然科学基金(21901215); 国家自然科学基金(21672030); 中央高校基本科研业务费专项资金(2682020CX53)

Studies on the Chemical Synthesis of Natural Drugs Berberine

Xifei Yan^a, Jianfeng Zheng^a(), Wei-Dong Z. Li^a^,^b()

a Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031
b Key Laboratory of Natural Product Chemistry and Application in Xinjiang, Yili Normal University, Yining, Xinjiang 835000

Received:2020-12-31 Revised:2021-01-26 Published:2021-02-26
Contact: Jianfeng Zheng, Wei-Dong Z. Li
Supported by:
National Natural Science Foundation of China(21901215); National Natural Science Foundation of China(21672030); Fundamental Research Funds for the Central Universities(2682020CX53); Key Program of Natural Science Foundation of Xinjiang Autonomous Region Colleges(XJEDU2018I018)

Berberine is an important natural drug and a kind of benzyl isoquinoline alkaloid, which has unique four-ring structure. In recent years, pharmacological research has found berberine is expected to be used in the clinical treatment of cancer, diabetes and other frequently occurring diseases. Based on the Woodward’s biosynthetic hypothesis, a schematic review on the synthetic studies towards berberine is provided.

Key words: natural drug, berberine, benzyl isoquinoline, total synthesis

Cite this article

Xifei Yan, Jianfeng Zheng, Wei-Dong Z. Li. Studies on the Chemical Synthesis of Natural Drugs Berberine[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2217-2227.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 14

Figure 1. Structures of berberine and its analogues

Scheme 1. Biosynthetic route of berberine

Scheme 2. Major biosynthesis routes of monoterpene indole alkaloids, the Robinson-Woodward’s biosynthetic hypothesis of monoterpene indole alkaloids and proposed major biosynthesis routes of berberine

Scheme 3. Strategies of total synthesis or formal synthesis of berberine

Scheme 4. Synthesis of framework of berberine with formaldehyde

Scheme 5. Synthesis of framework of berberine with other formylation reagent

Scheme 6. Synthesis of berberine and its framework using C1 intramolecular cyclization

Scheme 7. Synthesis of berberine and its framework using C2 intramolecular cyclization

Scheme 8. Total synthesis of berberine and its framework by An’s group et al.

Scheme 9. Synthesis of framework of berberine

Scheme 10. Metal-catalyzed total synthesis of berberine

Scheme 11. Formal synthesis of berberine skeleton by Li’s group

Figure 2. Structures of (–)-β-hydrastine and its analogues

分类	年份	研究组	步骤数^a	总收率^b/%	关键中间体		参考文献
分类	年份	研究组	步骤数^a	总收率^b/%	A	B	参考文献
C1环化法	1969	Kametani	>6	<8			[33]
C1环化法	2007	亚邦制药	6	67			[40]
C2环化法	1972	安静娴	7	6.4^c			[42]
C2环化法	2018	Clift	4	54			[52]
其它金属催化合成法	2014	Donohobe	7	28			[53]
	2015	Anand	4	32			[54]
	2016	童荣标	6	19			[55]
	2020	张延东	5	7.6			[57]

Table 1. Summary of total synthesis of berberine

References 61

[1]	Schulz, E. R. J. Am. Pharm. Assoc. 1926, 15,33.
[2]	(a) Eckhardt, K.; Zeller, K.-P.; Siehl, H.-U.; Berger, S.; Sicker, D. Chem. Unserer Zeit 2017, 51,344.
	(b) Buchner, J. A.; Herberger, J. E. Repert. Pharm. 1830, 36,1.
[3]	Abadi, B. E. A.; Moss, D. S.; Palmer, R. A. J. Crystallogr. Spectrosc. Res. 1984, 14,269.
[4]	Durairajan, S. S. K.; Liu, L.-F.; Lu, J.-H.; Chen, L.-L.; Yuan, Q J.; Chung, S. K.; Huang, L.; Li, X.-S.; Huang, J.-D.; Li, M. Neurobiol. Aging 2012, 33,2903.
[5]	Hong, Y.; Hui, S.-C.; Chan, T.-Y.; Hou, J.-Y. Am. J. Chin. Med. 2002, 30,589.
[6]	Kong, W. J.; Wei, J.; Abidi, P.; Lin, M.; Inaba, S.; Li, C.; Wang, Y. L.; Wang, Z. Z.; Si, S. Y.; Pan, H. N.; Wang, S. K.; Wu, J. D.; Wang, Y.; Li, Z. R.; Liu, J. W.; Jiang, J.-D. Nat. Med. 2004, 10,1344.
[7]	Lee, H. W.; Suh, J. H.; Kim, H.-N.; Kim, A. Y.; Park, S. Y.; Shin, C. S.; Choi, J.-Y.; Kim, J. B. J. Bone Miner. Res. 2008, 23,1227.
[8]	Xing, J.; He, H. World Latest Med. Inf. 2019, 19,231(in Chinese).
	(邢娟, 何梦静, 世界最新医学信息文摘, 2019, 19,231.)
[9]	Amin, A. H.; Subbaiah, T. V.; Abbasi, K. M. Can. J. Microbiol. 1969, 15,1067.
[10]	Cong, Z. Q. M.S Thesis, Shanghai Institute of Materia Media, Chinese Academy of Sciences, Shanghai, 2019(in Chinese).
	丛湛青, 硕士论文, 中国科学院上海药物研究所,上海, 2019) .
[11]	Liu, Y. Ph.D. Dissertation, East China Normal University, Shanghai, 2019(in Chinese).
	(刘艺, 博士论文, 华东师范大学, 上海, 2019.)
[12]	Sobolova, K.; Hrabinova, M.; Hepnarova, V.; Kucera, T.; Kobrlova, T.; Benkova, M.; Janockova, J.; Dolezal, R.; Prchal, L.; Benek, O.; Mezeiova, E.; Jun, D.; Soukup, O.; Korabecny, J. Eur. J. Med. Chem. 2020, 203,112593.
[13]	Zhang, L.; Shi, M. X.; Liu, J. F.; Han, W. N. J. Int. Pharm. Res. 2018, 45,325(in Chinese).
	(张龙, 史明星, 刘金凤, 韩维娜, 国际药学研究杂志, 2018, 45,325.)
[14]	Jung, H. A.; Min, B.-S.; Yokozawa, T.; Lee, J.-H.; Kim, Y. S.; Choi, J. S. Biol. Pharm. Bull. 2009, 32,1433.
[15]	Li, Y.-H.; Yang, P.; Kong, W.-J.; Wang, Y.-X.; Hu, C.-Q.; Zuo, Z.-Y.; Wang, Y.-M.; Gao, H.; Gao, L.-M.; Feng, Y.-C.; Du, N.-N.; Liu, Y.; Song, D.-Q.; Jiang, J.-D. J. Med. Chem. 2009, 52,492.
[16]	Xu, B. B.; Jiang, X. J.; Xiong, J.; Lan, J.; Tian, Y.; Zhong, L.; Wang, X. Q.; Xu, N.; Cao, H. W.; Zhang, W. Q.; Zhang, H.; Hong, X. T.; Zhan, Y.-Y.; Zhang, Y. D.; Hu, T. H. J. Med. Chem. 2020, 63,5841.
[17]	Gear, J. R.; Spenser, I. D. Can. J. Chem. 1963, 41,783.
[18]	Muller, M. J.; Zenk, M. H. Planta Med. 1992, 58,524.
[19]	Hashimoto, T.; Yamada, Y. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1994, 45,257.
[20]	Menéndez-Perdomo, I. M.; Facchini, P. J. Molecules 2018, 23,2899.
[21]	Beaudoin, G. A. W.; Facchini, P. J. Planta 2014, 240,19.
[22]	Wu, S. W.; Yang, M. Q.; Xiao, Y. L. Chin. J. Org. Chem. 2018, 38,2243(in Chinese).
	(吴世文, 杨盟权, 肖友利, 有机化学, 2018, 38,2243.)
[23]	Woodward, R. B. Nature 1948, 162,155.
[24]	Sato, F.; Yamada, Y. Phytochemistry 1984, 23,281.
[25]	(a) Gao, Y.; Yin, H.; Sun, Y. H.; Zhang, Z. Q.; Cui, Y. J. Fungal Res. 2008, 6,216(in Chinese).
	(高杨, 殷红, 孙宇宏, 张志强, 崔迎, 菌物研究, 2008, 6,216.)
	(b) Gao, Y.; Liu, M. Guangzhou Chem. Ind. 2012, 40,91(in Chinese).
	(高杨, 刘铭, 广州化工, 2012, 40,91.)
[26]	Liu, X. S. Hans J. Chem. Eng. Technol. 2020, 10,306(in Chinese).
	(刘雪松, 化学工程与技术, 2020, 10,306.)
[27]	Dominguez, X. A.; Delgado, J. G.; Reeves, W. P.; Gardner, P. D. Tetrahedron Lett. 1967, 8,2493.
[28]	Pictet, A.; Gams, A. Ber. Dtsch. Chem. Ges. 1911, 44,2480.
[29]	Buck, J. S.; Perkin, W. H. J. Chem. Soc., Trans. 1924, 125,1675.
[30]	Haworth, R. D.; Perkin, W. H.; Rankin, J. J. Chem. Soc., Trans. 1924, 125,1686.
[31]	Buck, J. S.; Perkin, W. H.; Stevens, T. S. J. Chem. Soc., Trans. 1925, 127,1462.
[32]	Buck, J. S.; Davis, R. M. J. Am. Chem. Soc. 1930, 52,660.
[33]	Kametani, T.; Noguchi, I.; Saito, K.; Kaneda, S. J. Chem. Soc. C 1969,2036.
[34]	Cutter, P. S.; Miller, R. B.; Schore, N. E. Tetrahedron 2002, 58,1471.
[35]	Mastranzo, V. M.; Romero, J. L. O.; Yuste, F.; Ortiz, B.; Sánchez-Obregón, R.. García Ruano, J.L. Tetrahedron 2012, 68,1266.
[36]	Makhey, D.; Gatto, B.; Yu, C.; Liu, A.; Liu, L. F.; LaVoie, E. J. Biorg. Med. Chem. 1996, 4,781.
[37]	Szawkalo, J.; Czarnocki, Z. Monatsh. Chem. 2005, 136,1619.
[38]	Miyazawa, M.; Tokuhashi, T.; Horibata, A.; Nakamura, T.; Onozaki, Y.; Kurono, N.; Senboku, H.; Tokuda, M.; Ohkuma, T.; Orito, K. J. Heterocycl. Chem. 2013, 50,E48.
[39]	Matulenko, M. A.; Meyers, A. I. J. Org. Chem. 1996, 61,573.
[40]	Chen, Z. X.; Tao, F.; Xia, Z. J.; Ma, S. M. CN 101245064, 2008.
[41]	Lee, D. Y. W.; Liu, J.; Zhang, S. Z.; Huang, P.; Liu-Chen, L.-Y. Bioorg. Med. Chem. Lett. 2017, 27,1437.
[42]	North-east Pharmaceutical Factory Chin. J. Pharm. 1972, (4),4(in Chinese).
	(东北制药总厂, 中国医药工业杂志, 1972, (4),4.)
[43]	(a) Chen, C.; Luo, Z. M.; Yang, H. J.; Feng, Y. C. Chin. J. Org. Chem. 2016, 36,1426(in Chinese).
	(陈程, 罗卓玛, 杨鸿均, 冯豫川, 有机化学, 2016, 36,1426.)
	(b) Chen, C.; X, M. M.; Zhao, Q.; Liu, C. X.; Yang, H. J.; Feng, Y. C. Chin. J. Org. Chem. 2017, 37,503(in Chinese).
	(陈程, 徐蒙蒙, 赵青, 刘承秀, 杨鸿均, 冯豫川, 有机化学, 2017, 37,503.)
[44]	Guangxi Nanning Pharmaceutical Factory Chin. J. Pharm. 1973, (7),4(in Chinese).
	(广西南宁制药厂, 中国医药工业杂志, 1973, (7),4.)
[45]	Chen, S. Q.; Lin, W. F.; Zang, J. H.; Liu, J. H.; Qi, S. H.; Zhang, L. Q.; Song, G. L. CN 1312250, 2001.
[46]	Tang, C. G. CN 106543171, 2017.
[47]	Feng, X.; Fu, L.; Zhao, C. A. CN 107868072, 2018.
[48]	Yasuda, S.; Hirasawa, T.; Hanaoka, M. Tetrahedron Lett. 1987, 28,2399.
[49]	Nimgirawath, S.; Ponghusabun, O. Aust. J. Chem. 1994, 47,951.
[50]	He, Y.; Zheng, Y.; Hai, L.; Wu, Y. Chin. J. Chem. 2014, 32,1121.
[51]	Garad, D. N.; Mhaske, S. B. Org. Lett. 2016, 18,3862.
[52]	Mori-Quiroz, L. M.; Hedrick, S. L.; De Los Santos, A. R.; Clift, M. D. Org. Lett. 2018, 20,4281.
[53]	Gatland, A. E.; Pilgrim, B. S.; Procopiou, P. A.; Donohoe, T. J. Angew. Chem., Int. Ed. 2014, 53,14555.
[54]	Reddy, V.; Jadhav, A. S.; Anand, R. V. Org. Biomol. Chem. 2015, 13,3732.
[55]	(a) Zhou, S. Q.; Tong, R. B. Chem.-Eur. J. 2016, 22,7084.
	(b) Yu, J. X.; Zhang, Z. H.; Zhou, S. Q.; Zhang, W.; Tong, R. B. Org. Chem. Front. 2018, 5,242.
[56]	Li, K.; Ou, J. J.; Gao, S. H. Angew. Chem., Int. Ed. 2016, 55,14778.
[57]	Jiang, X. J.; Zeng, Z. X.; Hua, Y. H.; Xu, B. B.; Shen, Y.; Xiong, J.; Qiu, H. J.; Wu, Y. F.; Hu, T. H.; Zhang, Y. D. J. Am. Chem. Soc. 2020, 142,15585.
[58]	Li, W.-D.Z.; Yang, H. Tetrahedron 2005, 61,5037.
[59]	Reimann, E.; Grasberger, F.; Polborn, K. Monatsh. Chem. 2003, 134,991.
[60]	Guo, W.-S. Ph.D. Dissertation, Nankai University, Tianjing, 2012(in Chinese).
	(郭维斯, 博士论文, 南开大学, 天津, 2012.)
[61]	Spenser, L. D.; Gear, J. R. J. Am. Chem. Soc. 1962, 84,1059.

天然药物小檗碱的化学合成研究进展

Studies on the Chemical Synthesis of Natural Drugs Berberine

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 14

References 61

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Xingzhou Liu, Mingjia Yu, Jianhua Liang. Research Progress on the Synthesis of Protoberberine Skeleton and Its Anti-inflammatory Activity [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1325-1340.
[2]	Jingping Hu, Wenqing Chen, Yuyang Jiang, Jing Xu. Synthesis of Tetracyclic Core Structure of Daphnezomines A and B [J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 171-177.
[3]	Xiangkai Kong, Yipeng Zhang, Lingjing Dang, Wen Chen, Hongbin Zhang. Research Progress in Synthesis of Indole Alkaloids Vindoline and Vindorosine [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2728-2744.
[4]	Ran Gao, Weisheng Tian. Synthesis of Azedarachol and 2α,3α,20R-Trihydroxypregnane-16β-methacrylate [J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2521-2526.
[5]	Mengmeng Xu, Quan Cai. Progress of Catalytic Asymmetric Diels-Alder Reactions of 2-Pyrones [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 698-713.
[6]	Jun Zhao, Jian Xiao, Yawen Wang, Yu Peng. Advances on the Synthesis of Natural Products with Dihydrobenzofuran Skeleton via Oxidative [3+2] Cycloadditions [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 2933-2945.
[7]	Minxin Li, Qiuping Zou, Wenrong Du, Jinchun Gao, Yanping Li, Zewei Mao. Total Synthesis and Anti-inflammatory Evaluation of Dorsmerunin A [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3292-3296.
[8]	Jian Xiao, Yu Peng, Wei-Dong Z. Li. Advances on the Total Synthesis of Sesquiterpenoid Alkaloid Dendrobine [J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2636-2649.
[9]	Ding Ma, Junli Ao, Naifeng Hu, Guangxin Liang. Progress in Biological Activity and Synthesis of Nematode Hatching Pheromone Glycinoeclepin A [J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 553-566.
[10]	Gang Yang, Xiangyu Feng, Congcong Han, Yang Chen, Shuzhong He. Synthesis of the ABC Ring System of Wallichanol Natural Product [J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 726-730.
[11]	Lu Guo, Pingping Tang. Recent Advance in the Synthesis of Natural Products of Schisandra Triterpenoid [J]. Chinese Journal of Organic Chemistry, 2021, 41(10): 3816-3825.
[12]	Han Jilai, Tang Meilin, Sun Xun. Study on the Total Synthesis of Resveratrol Dimers Quadrangularin A and Pallidol [J]. Chinese Journal of Organic Chemistry, 2020, 40(6): 1571-1577.
[13]	Dong Wei, Wang Xin, Ge Zemei, He Fang, Li Runtao. Efficient Synthesis of Wogonin [J]. Chinese Journal of Organic Chemistry, 2020, 40(6): 1725-1730.
[14]	Xie Tao, He Haibing, Gao Shuanhu. Synthetic Progress of Polycyclic Xanthone [J]. Chinese Journal of Organic Chemistry, 2020, 40(3): 551-562.
[15]	Sun Zezhong, Xu Miao, Wang Yunxia, Hu Xiangdong. Synthetic Progress of Alkaloids against Mycobacterium Tuberculosis: Pseudopteroxazole and Ileabethoxazole [J]. Chinese Journal of Organic Chemistry, 2020, 40(12): 4203-4215.