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2020 , Vol. 40 >Issue 6: 1409 - 1422

DOI: https://doi.org/10.6023/cjoc202003015

研究专题

P-手性膦配体促进的手性药物高效合成

  • 许容华 ,
  • 杨贺 ,
  • 汤文军
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  • a 上海科技大学物质科学与技术学院 上海 201210;
    b 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032;
    c 南方科技大学 深圳格拉布斯研究院 广东深圳 518055;
    d 国科大杭州高等研究院化学和材料科学学院 杭州 310024

收稿日期: 2020-03-06

  修回日期: 2020-04-06

  网络出版日期: 2020-04-17

基金资助

国家自然科学基金（No.21725205，21432007，21572246）、中国科学院战略性先导科技专项（XDB20000000）和王宽诚教育基金会资助项目.

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Efficient Synthesis of Chiral Drugs Facilated by P-Chiral Phosphorus Ligands

  • Xu Ronghua ,
  • Yang He ,
  • Tang Wenjun
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  • a School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210;
    b State Key Laboratory of Bio-Organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032;
    c Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, Guangdong 518055;
    d School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024

Received date: 2020-03-06

  Revised date: 2020-04-06

  Online published: 2020-04-17

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21725205, 21432007, 21572246), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000) and the K. C. Wong Education Foundation.

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摘要

发展高效实用的不对称催化反应对手性药物的简洁合成具有重要的意义，而手性配体和催化剂对于发展高效的不对称催化反应尤为关键.综述了基于苯并氧杂膦烷结构的P-手性单膦和双膦配体的设计理念以及它们在手性药物合成中的应用.这类配体具有P-手性、刚性，大位阻和富电子等结构特征，物理化学性质稳定，并且易于衍生化，在过渡金属催化的不对称氢化、偶联、环化和加成反应中表现出优异的催化性能.这些不对称催化反应的发展促进了一系列重要药物分子的高效不对称合成.

关键词： 手性膦配体; 苯并磷氧杂环; 不对称氢化; 不对称偶联; 手性药物

本文引用格式

许容华 , 杨贺 , 汤文军 . P-手性膦配体促进的手性药物高效合成[J]. 有机化学, 2020 , 40(6) : 1409 -1422 . DOI: 10.6023/cjoc202003015

Abstract

Development of efficient and practical asymmetric catalytic reactions plays a pivotal role for the concise syntheses of chiral drugs. Chiral ligands and catalysts are crucial for the selectivity and reactivity of the catalytic reactions. In this account, the design and development of a series of P-chiral mono- and bis-phosphorus ligands were summarized based on a benzooxaphosphane backbone and their applications in the synthesis of chiral drugs. Beside their P-chirality, these ligands are structurally rigid, sterically bulky, and electron-rich, providing good physical properties and tunabilities. Facilitated by these chiral ligands, a series of efficient and practical reactions including asymmetric hydrogenation, asymmetric cross-coupling, asymmetric cyclization, and asymmetric nucleophilic additions have been developed. The excellent conversions, yields, regioselectivities, enantioselectivities, and broad substrate scope have enabled concise and efficient syntheses of a series of chiral drugs.

Key words： chiral phosphorus ligands; transition metal catalysis; asymmetric synthesis; enantioselectivity; chiral drugs

参考文献

[1] Lin, G. Q.; Wang, M. X. Chiral Synthesis and Chiral Drugs, Chemical Industry Press, Beijing, 2008, pp. 1~4(in Chinese). (林国强, 王梅祥, 手性合成和手性药物, 化学工业出版社, 北京, 2008, pp. 1~4.)
[2] Lin, G. Q.; Sun, X. W.; Chen, Y. Q.; Li, Y. M.; Chen, X. Z. Chiral Synthesis-Asymmetric Reactions and Their Applications, Science Press, Beijing, 2013, pp. 36~38(in Chinese). (林国强, 孙兴文, 陈耀全, 李月明, 陈新滋, 手性合成——不对称反应及其应用, 科学出版社, 北京, 2013, pp. 36~38.)
[3] Tang, W; Zhang, X. Chem. Rev. 2003, 103, 3029.
[4] Tang, W. In Proceedings of the 11th National Conference on Natural Organic Chemistry of the Chinese Chemical Society, Volume 1, Shanghai, 2019, p. 71(in Chinese). (汤文军, 中国化学会第十一届全国天然有机化学学术会议论文集, 第一册, 上海, 2019, p. 71.)
[5] (a) Xu, G.; Senanayake, C. H; Tang, W. Acc. Chem. Res. 2019, 52, 1601.
(b) Wu, T.; Xu, G.; Tang, W. Aldrichim. Acta 2020, 53, 27.
(c) Tang, W.; Li, K. Strem Chem. 2019, XXXI, 1.
[6] Liu, G.; Liu, X.; Cai, Z.; Jiao, G.; Xu, G.; Tang, W. Angew. Chem., Int. Ed. 2013, 52, 42359.
[7] Li, C.; Wan, F; Chen, Y.; Peng, H.; Tang, W.; Yu, S.; McWilliams, H. C.; Mustakis, J.; Samp, L.; Maguire, R. J. Angew. Chem., Int. Ed. 2019, 58, 13573.
[8] Daniella M. S.; Yuka K.; Alejandro V.; Michael W.; Massimo G.; John J. O. Nat. Rev. Drug Discovery 2017, 16, 843.
[9] Patil, Y. S.; Bonde, N. L.; Kekan, A. S.; Sathe, D. G.; Das, A. Org. Process Res. Dev. 2014, 18, 1714.
[10] Zhu, J.; Huang, L.; Dong, W.; Li, N.; Yu, X.; Deng, W.; Tang, W. Angew. Chem., Int. Ed. 2019, 58, 16119.
[11] Rottmann, M.; McNamara, C.; Yeung, B. K. S. Science 2010, 329, 1175.
[12] Huang, L.; Zhu, J.; Jiao, G.; Wang, Z.; Yu, X.; Deng, W.; Tang W. Angew. Chem., Int. Ed. 2016, 55, 4527.
[13] Dhillon, S.; Scott, L. J.; Plosker, G. L. CNS Drugs 2006, 20, 763.
[14] Yang, H.; Tang, W. Chem. Rec. 2020, 20, 23.
[15] Cao, Z.; Du, K.; Liu, J. H.; Tang, W. Tetrahedron 2016, 72, 1782.
[16] Li, B.; Li, T.; Aliyu, M. A.; Li, Z.; Tang, W. Angew. Chem., Int. Ed. 2019, 58, 11355.
[17] Dodou, K.; Anderson, R. J.; Lough, W. J.; Small, D. A. P.; Shelley, M. D.; Groundwater, P. W. Bioorg. Med. Chem. 2005, 13, 4228.
[18] (a) Xu, G.; Fu, W.; Liu, G.; Senanayake, C. H.; Tang, W. J. Am. Chem. Soc. 2014, 136, 570.
(b) Xu, G.; Zhao, Q.; Tang, W. Chin. J. Org. Chem. 2014, 34, 1919(in Chinese). (徐广庆, 赵庆, 汤文军, 有机化学, 2014, 34, 1919.)
[19] Yang, H.; Sun, J.; Gu, W.; Tang, W. J. Am. Chem. Soc. 2020, 142, 8036.
[20] Lu, Y.; Dong, C.; Huang, J.; Zhou, H.; Wang, W. Future Med. Chem. 2017, 9, 1243.
[21] Fandrick, K. R.; Li, W.; Zhang, Y.; Tang, W.; Gao, J.; Rodriguez, S.; Patel, N. D.; Reeves, D. C.; Wu, J.-P.; Sanyal, S.; Gonnella, N.; Qu, B.; Haddad, N.; Lorenz, J. C.; Sidhu, K.; Wang, J.; Ma, S.; Grinberg, N.; Lee, H.; Tsantrizos, Y.; Poupart, M.-A.; Busacca, C. A.; Yee, N. K.; Lu, B. Z.; Senanayake, C. H. Angew. Chem., Int. Ed. 2015, 54, 7144.
[22] Haddad, N.; Mangunuru, H. P. R.; Fandrick, K. R.; Qu, B.; Sieber, J. D.; Rodriguez, S.; Desrosiers, J. N.; Patel, N. D.; Lee, H.; Kurouski, D.; Grinberg, N.; Yee, N. K.; Song, J. J.; Senanayake, C. H. Adv. Synth. Catal. 2016, 358, 3522.
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