含氟药物研究进展和芳(杂)环氟化及N(n=1,2,3)氟甲基化新方法

doi:10.6023/cjoc201310039

摘要/Abstract

论述了最近几年含氟药物的最新研究成果和含氟新药的研究概况，从药物化学工作者的角度对芳（杂环）的氟化反应，氟甲基化、二氟甲基化和三氟甲基化反应进展和亮点做了分析归纳和总结，对一些金属催化的氟化新反应的机理进行了简单的阐述. 指出药物结构优化中充分利用氟化学的最新研究成果是一条值得探索的捷径.

关键词: 氟, 含氟药物, 氟化反应, 三氟甲基化, 二氟甲基化, 一氟甲基化, 药物设计

This review outlines the recent advances of fluorinated drugs and latest research overview from the perspective of a medicinal chemist wherein the synthesis and use of trifluoromethylation, difluoromethylation, monofluoromethylation and fluorinated aromatic (heterocyclic) compounds are highlighted. It is pointed out that the full use of the latest progress in fluorine chemistry provides a shortcut to new fluorinated compounds or previously difficult to prepare compounds which is worth exploring for drug discovery.

Key words: fluorine, fluorinated drugs, fluorination, trifluoromethylation, difluoromethylation, monofluoromethylation, drug design

引用此文

张霁, 金传飞, 张英俊. 含氟药物研究进展和芳(杂)环氟化及N(n=1,2,3)氟甲基化新方法[J]. 有机化学, 2014, 34(4): 662-680.

Zhang Ji, Jin Chuanfei, Zhang Yingjun. Recent Advances in Research and Development of Fluorinated Drugs and New Methods for Fluorination, Mono-, Di-and Tri-fluoromethylation[J]. Chin. J. Org. Chem., 2014, 34(4): 662-680.

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参考文献

[1] Wang, J.; Liu, H. Chin. J. Org. Chem. 2011, 31, 1785 (in Chinese).(王江, 柳红, 有机化学, 2011, 31, 1785.)

[2] (a) Wang, J.; Sanchez, M.; Acena, J.; Pozo, C.; Sorochinsky, A.; Fustero, S.; Soloshonok, V.; Liu, H. Chem. Rev. 2014, 114, 2432.(b) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529.

[3] Krik, K. L. Org. Process Res. Dev. 2008, 12, 305.

[4] Ojima, I. J. Org. Chem. 2013, 78, 6358.

[5] (a) Qing, F. L. Chin. J. Org. Chem. 2012, 32, 815 (in Chinese).(卿凤翎, 有机化学, 2012, 32, 815.) (b) Ritter, S. K. Chem. Eng. News 2012, 90, 10.(c) Thayer, A. M. Chem. Eng. News 2006, 84, 15.

[6] (a) Cui, J. J.; Tran, M.; Shen, H.; Nambu, M.; Kung, P. P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I.; Mc, M.; Grodsky, N.; Ryan, K.; Padrique, E.; Alton, G.; Timofeevski, S.; Yamazaki, S.; Li, Q.; Zou, H.; Christensen, J.; Mroczkowski, B.; Bender, S.; Kania, R. S.; Edwards, M. P. J. Med. Chem. 2011, 54, 6342.(b) Li, J.; Cai, Y.; Chen, W.; Liu, X.; Lin, L.; Feng, X. J. Org. Chem. 2012, 77, 9148.

[7] Hansen, K. B.; Hsiao, Y.; Xu, F.; Rivera, N.; Clausen, A.; Kubryk, M.; Krska, S.; Rosnea, T.; Simmons, B.; Balsells, J.; Ikemoto, N.; Sun, Y.; Spindler, F.; Malan, C.; Grabowski, E. J. J.; Armstrong, J. D. J. Am. Chem. Soc. 2009, 131, 8798.

[8] (a) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.(b) Ichikawa, M.; Ohtsuka, M.; Ohki, H.; Ota, M.; Haginoya, N.; Itoh, M.; Shibata, Y.; Sugita, K.; Ishigai, Y.; Terayama, K.; Kanda, A.; Usui, H. ACS Med. Chem. Lett. 2013, 4, 932.

[9] Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134.

[10] Wang, X.; Mei, T. S.; Yu, J. Q. J. Am. Chem. Soc. 2009, 131, 7520.

[11] Chan, K. S. L.; Wasa, M.; Wang, X.; Yu, J. Q. Angew. Chem., Int. Ed. 2011, 50, 9081.

[12] Truong, T.; Klimovica, K.; Daugulis, O. J. Am. Chem. Soc. 2013, 135, 9342.

[13] Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 4648.

[14] Fier, P. S.; Luo, J.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 2559.

[15] (a) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060.(b) Mazzotti, A. R.; Campbell, M. G.; Tang, P.; Murphy, J. M.; Ritter, T. J. Am. Chem. Soc. 2013, 135, 14012.

[16] Ye, Y.; Schimler, S. D.; Hanley, P. S.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 16292.

[17] Cazorla, C.; Metay, E.; Andrioletti, B.; Lemaire, M. Tetrahedron Lett. 2009, 50, 3936.

[18] Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860.

[19] Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem. Soc. 2009, 131, 1662.

[20] (a) Tang, P.; Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2010, 132, 12150.(b) Lee, E.; Hooker, J. M.; Ritter, T. J. Am. Chem. Soc. 2012, 134, 17456.(c) Gao, Z.; Lim, Y. H.; Tredwell, M.; Li, L.; Verhoog, S.; Hopkinson, M.; Kaluza, W.; Collier, T. L.; Passchier, J.; Huiban, M.; Gouverneur, V. Angew. Chem., Int. Ed. 2012, 51, 6733.

[21] Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 10795.

[22] Sun, H.; Dimagno, S. G. Angew. Chem., Int. Ed. 2006, 45, 2720.

[23] Kumai, S.; Seki, T.; Wada, A. JP 04164068, 1992[Chem. Abstr. 1992, 117, 233865].

[24] Grushin, V. V.; Marshall, W. J. Organometallics 2008, 27, 4825.

[25] Tang, P.; Wang, W.; Ritter, T. J. Am. Chem. Soc. 2011, 133, 11482.

[26] Wannberg, J.; Wallinder, C.; Unlusoy, M.; Skold, C.; Larhed, M. J. Org. Chem. 2013, 78, 4184.

[27] Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130, 13552.

[28] Nemoto, H.; Nishiyama, T.; Akai, S. Org. Lett. 2011, 13, 2714.

[29] Adachi, K.; Ohira, Y.; Tomizawa, G.; Ishihara, S.; Oishi, S. J. Fluorine Chem. 2003, 120, 173.

[30] Tian, T.; Zhong, W. H.; Meng, S.; Meng, X. B.; Li, Z. J. J. Org. Chem. 2013, 78, 728.

[31] Ichiishi, N.; Canty, A. J.; Yates, B. F.; Sanford, M. S. Org. Lett. 2013, 15, 5134.

[32] Olberg, D. E.; Arukwe, J. M.; Grace, D.; Hjelstuen, O. K.; Solbakken, M.; Kindberg, G. M.; Cuthbertson, A. J. Med. Chem. 2010, 53, 1732.

[33] Hu, J.; Zhang, W.; Wang, F. Chem. Commun. 2009, 45, 7465.

[34] Narjes, F.; Koehler, K. F.; Koch, U.; Gerlach, B.; Colarusso, S.; Steinkuhler, C.; Brunetti, M.; Altamura, S.; De, F. R.; Matassa, V. G. Bioorg. Med. Chem. Lett. 2002, 12, 701.

[35] Chowdhury, M. A.; Abdellatif, K. R. A.; Dong, Y.; Das, D.; Suresh, M. R.; Knaus, E. E. J. Med. Chem. 2009, 52, 1525.

[36] Fujiwara, Y.; Dixon, J. A.; Rodrigue, R. A.; Baxter, R. D.; Dixon, D. D.; Collins, M. R.; Blackmond, D. G.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 1494.

[37] Fujiwara, Y.; Dixon, J. A.; Hara, F.; Funder, E. D.; Dixon, D. D.; Rodrigue, R. A.; Baxter, R. D.; Herle, B.; Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95.

[38] Xia, J. B.; Zhu, C.; Chen, C. J. Am. Chem. Soc. 2013, 135, 17494.

[39] Fujikawa, K.; Fujioka, Y.; Kobayashi, A.; Amii, H. Org. Lett. 2011, 13, 5560.

[40] Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 5524.

[41] Mcmurtrey, K. B.; Racowski, J. M.; Sanford, M. S. Org. Lett. 2012, 14, 4094.

[42] Wang, X.; Zhang, Y.; Wang, J. B. Sci. Sin. Chim. 2012, 42, 1417 (in Chinese).(王兮, 张艳, 王剑波, 中国科学: 化学, 2012, 42, 1417.)

[43] Tomashenko, O. A.; Grushin. V. V. Chem. Rev. 2011, 111, 4475.

[44] (a)Wu, X. F.; Neumann, H.; Beller, M. Chem-Asian J. 2012, 7, 1744.(b) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470.(c) Liu, H.; Gu, Z.; Jiang, X. Adv. Synth. Catal. 2013, 355, 617.

[45] Ji, Y.; Brueckl, T.; Baxter, R. D.; Fujiwara, Y.; Seiple, I. B.; Su, S.; Blackmond, D. G.; Baran, P. S.; Baran, P. S. Proceedings of the National Academy of the Sciences of the United States of America, 2011, 108, 14411.

[46] (a) Langlois, B. R.; Laurent, E. R. N. Tetrahedron Lett. 1991, 32, 7525.(b) Langlois, B. R.; Laurent, E. R. N. Tetrahedron Lett. 1992, 33, 1291.

[47] (a) Ye, Y.; Kunzi, S. A.; Sanford, M. S. Org. Lett. 2012, 14, 4979.(b) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2012, 134, 9034.

[48] Novak, P.; Lishchynskyi, A.; Grushin, V. V. Angew. Chem., Int. Ed. 2012, 51, 7767.

[49] Dai, J. J.; Fang, C.; Xiao, B.; Yi, J.; Xu, J.; Liu, Z. J.; Lu, X.;Liu, L.; Fu, Y. J. Am. Chem. Soc. 2013, 135, 8436.

[50] Danoun, G.; Bayarmagnai, B.; Grunberg, M. F.; Gooβen, L. J. Angew. Chem., Int. Ed. 2013, 52, 7972.

[51] Wang, X.; Xu, Y.; Mo, F.; Ji, G.; Qiu, D.; Feng, J.; Ye, Y.; Zhang, S.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2013, 135, 10330.

[52] Nagib, D. A.; MacMillan, D. W. C. Nature 2011, 480, 224.

[53] Chu, L.; Qing, F. L. J. Am. Chem. Soc. 2012, 134, 1298.

[54] Liu, T.; Shao, X.; Wu, Y.; Shen, Q. Angew. Chem., Int. Ed. 2012, 51, 540.

[55] Zhang, C. P.; Wang, Z. L.; Chen, Q. Y.; Zhang, C. T.; Gu, Y. C.; Xiao, J. C. Angew. Chem., Int. Ed. 2011, 50, 1896.

[56] Mu, X.; Chen, S.; Zhen, X.; Liu, G. Chem. Eur. J. 2011, 17, 6039.

[57] Fu, D.; Zhang, J.; Cao, S. J. Fluorine Chem. 2013, 156, 170.

[58] Zeng, Y.; Zhang, L.; Zhao, Y.; Ni, C.; Zhao, J.; Hu, J. J. Am. Chem. Soc. 2013, 135, 2955.

[59] Wang, X.; Truesdale, L.; Yu, J. J. Am. Chem. Soc. 2010, 132, 3648.

[60] Su, D. B.; Duan, J. X.; Chen, Q. Y. Tetrahedron Lett. 1991, 32, 7689.

[61] Mulder, J. A.; Frutos, R. P.; Patel, N. D.; Qu, B.; Sun, X.; Tampone, T. G.; Gao, J.; Sarvestani, M.; Eriksson, M. C.; Haddad, N.; Shen, S.; Song, J.; Senanayake, C. H. Org. Process Res. Dev. 2013, 17, 940.

[62] (a) Zhang, J.; Morton, H. E.; Ji, J. Tetrahedron Lett. 2006, 47, 8733.(b) Kerdesky, F. A. J.; Leanna, M. R.; Zhang, J.; Li, W.; Lallaman, J. E.; Ji, J.; Morton, H. E. Org. Process Res. Dev. 2006, 10, 512.

[63] Zhao, Y.; Zhu, L.; Provencal, D. P.; Miller, T. A.; Bryan, C.; Langston, M.; Shen, M.; Bailey, D.; Sha, D.; Palmer, T.; Ho, T.; Li, M. Org. Process Res. Dev. 2012, 16, 1652.

[64] Witt, A.; Teodorovic, P.; Linderberg, M.; Johansson, P.; Minidis, A. Org. Process Res. Dev. 2013, 17, 672.

[65] (a) Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology, Wiley-Blackwell, 2009.(b) Petrov, V. A. Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and Applications, Wiley, 2009.(c) Roesky, H. W.; Sharpless, K. B. Efficient Preparation of Fluorine Compounds, Wiley, New Jersey, 2012.(d) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd, Completely Revised and Enlarged Edition, Wiley-VCH, Weinheim, 2013.

[66] (a) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214.(b) Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950.(c) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160.(d) Pan, F.; Shi, Z. Acta Chim. Sinica 2012, 70, 1679 (in Chinese).(潘菲, 施章杰, 化学学报, 2012, 70, 1679.)(e) He, Z.; Huang, Y.; Verpoort, F. Acta Chim Sinica 2013, 71, 700 (in Chinese).(何展荣, 黄毅勇, Verpoort Francis, 化学学报, 2013, 71, 700.)(f) Yang, Y.; You, Z.; Qing, F. Acta Chim. Sinica 2012, 70, 2323 (in Chinese).(杨义, 游正伟, 卿凤翎, 化学学报, 2012, 70, 2323.)

[67] (a) Zhang, J.; Sarma, K. D.; Curran, T. T. Synlett 2013, 0550.(b) Zhang, J.; Zhang, Y. J. Chin. J. Org. Chem. 2013, 33, 409 (in Chinese).(张霁, 张英俊, 有机化学, 2013, 33, 409.)