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

doi:10.6023/cjoc202406048

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (3): 1021-1029.DOI: 10.6023/cjoc202406048 Previous Articles Next Articles

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对映发散性合成(+)-和(–)-Crispine A

王艳本^a, 林祖铭^a, 黄莎华^a^,^*(), 朱莉莉^b, 洪然^b^,^*()

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

收稿日期:2024-06-29 修回日期:2024-08-22 发布日期:2024-09-26
作者简介:
^†共同第一作者
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)

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

Yanben Wang^a, Zuming Lin^a, Sha-Hua Huang^a(), Lili Zhu^b, Ran Hong^b()

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

Received:2024-06-29 Revised:2024-08-22 Published:2024-09-26
Contact: * E-mail: shahua@sit.edu.cn; rhong@sioc.ac.cn
About author:
^†(These authors contributed equally to this work).
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)

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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

Cite this article

Yanben Wang, Zuming Lin, Sha-Hua Huang, Lili Zhu, Ran Hong. Enantiodivergent Synthesis of (+)- and (–)-Crispine A[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 1021-1029.

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Fig. & Tab. 6

References 30

[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.

Entry	Lipase (U)	Solvent	Conv.^b/%	Time/h	ee^c/% (yield^b/%)		E factor^d
Entry	Lipase (U)	Solvent	Conv.^b/%	Time/h	(+)-6a	(–)-7a	E factor^d
1	CAL-B (100)	THF	32	6	36.6 (32)	96.6 (68)	82
2	CAL-B (100)	EtOAc	45	4	76.6 (45)	96.1 (55)	117
3	CAL-B (100)	Et₂O	52	4	96.6 (52)	88.8 (48)	68
4	CAL-B (100)	2-Me-THF	45	4	70.1 (45)	98.4 (55)	>200
5	CAL-B (25)	2-Me-THF	51	48	96.1 (51)	96.0 (49)	195
6	CAL-B (10)	2-Me-THF^e	49	42	87.2 (49)	96.7 (51)	170
7	CAL-B (25)	2-Me-THF^f	51	60	97.5 (51)	93.5 (49)	130

Entry	Lipase (U)	Solvent	Conv.^b/%	Time/h	ee^c/% (yield^b/%)		E factor^d
Entry	Lipase (U)	Solvent	Conv.^b/%	Time/h	(+)-6a	(–)-7a	E factor^d
1	CAL-B (100)	THF	32	6	36.6 (32)	96.6 (68)	82
2	CAL-B (100)	EtOAc	45	4	76.6 (45)	96.1 (55)	117
3	CAL-B (100)	Et₂O	52	4	96.6 (52)	88.8 (48)	68
4	CAL-B (100)	2-Me-THF	45	4	70.1 (45)	98.4 (55)	>200
5	CAL-B (25)	2-Me-THF	51	48	96.1 (51)	96.0 (49)	195
6	CAL-B (10)	2-Me-THF^e	49	42	87.2 (49)	96.7 (51)	170
7	CAL-B (25)	2-Me-THF^f	51	60	97.5 (51)	93.5 (49)	130

对映发散性合成(+)-和(–)-Crispine A

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

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