SIOC English
有机化学
高级检索

有机化学 >

2025 , Vol. 45 >Issue 3: 1021 - 1029

DOI: https://doi.org/10.6023/cjoc202406048

研究论文

对映发散性合成(+)-和(–)-Crispine A

  • 王艳本 ,
  • 林祖铭 ,
  • 黄莎华 ,
  • 朱莉莉 ,
  • 洪然
展开
  • a 上海应用技术大学化学与环境工程学院 上海 202418
    b 中国科学院上海有机化学研究所 生命过程小分子调控全国重点实验室 上海 200032
†共同第一作者

收稿日期: 2024-06-29

  修回日期: 2024-08-22

  网络出版日期: 2024-09-27

基金资助

国家自然科学基金(22271194); 国家自然科学基金(22371295); 国家自然科学基金(U24A20484); 上海市科学技术委员会(20XD1404700)

收起

Enantiodivergent Synthesis of (+)- and (–)-Crispine A

  • Yanben Wang ,
  • Zuming Lin ,
  • Sha-Hua Huang ,
  • Lili Zhu ,
  • Ran Hong
Expand
  • a School of Environmental and Chemical Engineering, Shanghai Institute of Technology, Shanghai 201418
    b State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
†(These authors contributed equally to this work).
* E-mail: ;
* E-mail: ;

Received date: 2024-06-29

  Revised date: 2024-08-22

  Online published: 2024-09-27

Supported by

National Natural Science Foundation of China(22271194); National Natural Science Foundation of China(22371295); National Natural Science Foundation of China(U24A20484); Science and Technology Commission of Shanghai Municipality(20XD1404700)

Fold

摘要

Crispine A是一种包含吡咯[2,1-a]异喹啉骨架的代表性生物碱, 具有多种生理活性. 利用立体选择性1,3-偶极环加成和酶催化动力学拆分, 实现了对crispine A的对映发散性合成. 研究发现, N—O键断裂并进一步环化可以高效构建该类活性生物碱的[2,1-a]异喹啉骨架. 合成过程中关键的酶拆分策略的运用也为很多包含四氢异喹啉吡咯烷类结构的活性天然产物合成提供新的思路.

关键词： 化学酶合成; 偶极环加成; 对映发散性合成; 动力学拆分; 硝酮

本文引用格式

王艳本 , 林祖铭 , 黄莎华 , 朱莉莉 , 洪然 . 对映发散性合成(+)-和(–)-Crispine A[J]. 有机化学, 2025 , 45(3) : 1021 -1029 . DOI: 10.6023/cjoc202406048

Abstract

Crispine A is a representative alkaloid bearing pyrrolo[2,1-a]isoquinoline to exhibit various biological activities. In this report, enantiodivergent synthesis of crispine A has been achieved, featuring a stereoselective 1,3-dipolar cycloaddition and an enzymatic kinetic resolution. The sequential process including cleavage of the N—O bond and cyclization proved to be effective and practical toward pyrrolo[2,1-a]isoquinoline in intriguing bioactive alkaloids. The capacity of enzymatic resolution dictated in this work is of great interest to accumulate the tetrahydroisoquinoline (THIQ)-fused pyrrolidine which is commonly embedded in various bioactive compounds.

Key words： chemoenzymatic synthesis; dipolar cycloaddition; enantiodivergent synthesis; kinetic resolution; nitrone

参考文献

[1]
Chrzanowska, M.; Grajewska, A.; Rozwadowska, M. D. Chem. Rev. 2016, 116, 12369 and earlier reviews cited therein.
[2]
Kim, A. N.; Ngamnithiporn, A.; Du, E.; Stoltz, B. M. Chem. Rev. 2023, 123, 9447.
[3]
Tao, S.; Wang, Y.; Hong, R.; Huang, S.-H. Molecules 2022, 27, e4324.
[4]
Matveeva, M. D.; Purgatorio, R.; Voskressensky, L. G.; Altomare, C. D. Future Med. Chem. 2019, 11, 2735.
[5]
Fahmy, N. M.; Al-Sayed, E.; El-Shazly, M.; Singab, A. N. Nat. Prod. Res. 2020, 34, 1891.
[6]
Fukuda, T.; Ishibashi, F.; Iwao, M. Lamellarin alkaloids: Isolation, synthesis, and biological activity. In The Alkaloids: Chemistry and Biology, Ed.: Knölker, H.-J., Academic Press, London 83, pp. 1-112.
[7]
Cui, H.-L. Org. Biomol. Chem. 2022, 20, 2779.
[8]
Zhang, Q.; Tu, G.; Zhao, Y.; Cheng, T. Tetrahedron 2002, 58, 6795.
[9]
Child, R.; Pyman, F. L. J. Chem. Soc. 1931, 36.
[10]
Mohan, C.; R. Krishna, B.; Sivanandan, S. T.; Ibnusaud, I. Eur. J. Org. Chem. 2021, 4911.
[11]
Yang, L.; Li, J.; Xu, Z.; Yao, P.; Wu, Q.; Zhu, D.; Ma, Y. Org. Lett. 2022, 24, 6531.
[12]
Szawkało, J.; Zawadzka, A.; Wojtasiewicz, K.; Leniewski, A.; Drabowiczb, J.; Czarnocki, Z. Tetrahedron: Asymmetry 2005, 16, 3619.
[13]
Yu, H.-H.; Yu, Z.-P.; Capon, R. J.; Zhang, H. Molecules 2022, 27, e1279.
[14]
Huang, S.-H.; Li, W.; Chen, L.; Xu, J.; Hong, R. Bioresour. Bioprocess. 2015, 2, e10.
[15]
Li, W.; Lin, Z.; Chen, L.; Tian, X.; Wang, Y.; Huang, S.-H.; Hong, R. Tetrahedron Lett. 2016, 57, 603.
[16]
Yang, L.; Lin, Z.; Shao, S.; Zhao, Q.; Hong, R. Angew. Chem. Int. Ed. 2018, 57, 16200.
[17]
Yang, L.; Lin, Z.; Zheng, K.; Kong, L.; Hong, R. Chin. J. Chem. 2020, 38, 725.
[18]
Peng, Y.; Lin, Z.; Zhu, L.; Han, S.; Huang, S.-H.; Hong, R. Chin. J. Chem. 2024, 42, 841.
[19]
Murahashi, S.-I.; Imada, Y. Chem. Rev. 2019, 119, 4684.
[20]
Tufariello, J. J. Acc. Chem. Res. 1979, 12, 396.
[21]
Confalone, P. N.; Huie, E. M. The [3+2] nitrone-olefin cycloaddition reaction In Organic Reactions, Vol. 36, Ed.: Kende, A. S., John Wiley & Sons, 1988, pp. 1-173.
[22]
Zhao, B. X.; Yu, Y.; Eguchi, S. Org. Prep. Proc. Int. 1997, 29, 185.
[23]
Brandi, A.; Cardona, F.; Cicchi, S.; Cordero, F. M.; Goti, A. [3+2] dipolar cycloadditions of cyclic nitrones with alkenes In Organic Reactions, Vol. 94, Ed.: Denmark, S. E., John Wiley & Sons, 2017, pp. 1-529.
[24]
Gotor-Fermández, V.; Busto, E.; Gotor, V. Adv. Synth. Catal. 2006, 348, 797.
[25]
Greenhalgh, M. D.; Taylor, J. E.; Smith, A. D. Tetrahedron 2018, 74, 5554.
[26]
Schmid, H.; Karrer, P. Helv. Chim. Acta 1949, 32, 1371.
[27]
Forró, E.; Schönstein, L.; Fülöp, F. Tetrahedron: Asymmetry 2011, 22, 1255.
[28]
Orsy, G.; Forró, E. Molecules 2023, 28, e6362.
[29]
Wang, J.; Gong, F.; Liang, T.; Xie, Z.; Yang, Y.; Cao, C.; Gao, J.; Lu, T.; Chen, X. Eur. J. Med. Chem. 2021, 225, 113815.
[30]
Tian, X.; Xuan, T.; Gao, J.; Zhang, X.; Liu, T.; Luo, F.; Pang, R.; Shao, P.; Yang, Y.-F.; Wang, Y. Nat. Commun. 2024, 15, 6429.
Options
文章导航

/

〈 〉