Synthetic Study of Kuroshine Alkaloids

doi:10.6023/cjoc202409012

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (3): 977-987.DOI: 10.6023/cjoc202409012 Previous Articles Next Articles

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Kuroshine类生物碱的合成研究

文国恩^a, 谷硕^a, 何海兵^a, 高栓虎^a^,^b^,^*()

a 华东师范大学化学与分子工程学院石油化工分子转化与过程全国重点实验室上海市绿色化学与化工过程绿色化重点实验室上海 200062
b 上海市分子智造前沿科学基地上海 200062

收稿日期:2024-09-11 修回日期:2024-10-16 发布日期:2024-12-05
基金资助:
国家高新技术研究发展计划(2022YFC2804201); 国家自然科学基金(22225105); 上海市科学技术委员会(22JC1401101)

Synthetic Study of Kuroshine Alkaloids

Guoen Wen^a, Shuo Gu^a, Haibing He^a, Shuanhu Gao^a^,^b()

a Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062
b Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, Shanghai 200062

Received:2024-09-11 Revised:2024-10-16 Published:2024-12-05
Contact: * E-mail: shgao@chem.ecnu.edu.cn
Supported by:
National High Technology Research and Development Program of China(2022YFC2804201); National Natural Science Foundation of China(22225105); Shanghai Science and Technology Committee(22JC1401101)

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Abstract

Kuroshine alkaloids are highly oxidized marine natural products isolated from Zoanthus, which have complex and diverse structure, including three all carbon quaternary carbon centers (C-9, C-12, and C-22), densely functional groups, and a highly oxidized skeleton. The main syntheic challenges include the construction of the fully hydrogenated phenanthrene A-B-C ring, the construction of adjacent quaternary carbon centers (C-9, C-22), and the precise introduction of oxidation states at C-11, C-28, and C-25 positions. A synthetic study on kuroshine alkaloids was conducted, successfully introducing the C-25 oxidation state through the addition of chloromethyl lithium to enone and epoxide rearrangement, and constructing adjacent quaternary carbon centers (C-9, C-22) through intramolecular alkylation substitution reactions. The C-12 oxidation state was introduced through a single electron epoxide opening mediated by samarium iodide. The synthesis of bicyclic aldehyde fragment 19 and chiral iodo fragment 20 was finally completed.

Key words: high oxidation state, alkylation, kuroshine alkaloid, marine natural product

Cite this article

Guoen Wen, Shuo Gu, Haibing He, Shuanhu Gao. Synthetic Study of Kuroshine Alkaloids[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 977-987.

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Fig. & Tab. 6

Figure 1. (A~C) Representative zoanthamine alkaloids and (D) high oxidation state natural products

Scheme 1. Total synthesis of norzoanthamine

Scheme 2. Our previous synthetic studies of norzoanthamine and synthetic plan of kuroshine alkaloids

Scheme 3. Synthesis of fragment 19

Entry	Base	Solvent	T/℃	Product
1	KHMDS	Toluene	0	27β (only 35%)
2	KHMDS	Toluene	r.t.	27β (only 46%)
3	t-BuOK	Toluene	60	27α+27β (dr=1∶3.0, 58%)
4	KHMDS	Toluene	60	27α+27β (dr=1∶2.4, 60%)
5	KHMDS	Toluene	100	27α+27β (dr=1∶2.3, 58%)
6	KHMDS	THF	60	27α+27β (dr=1∶1.3, 77%)
7	KHMDS	THF	100	27α+27β (dr=1∶1.1, 89%)

Table 1. Optimization of alkylation reaction

Scheme 4. Synthesis of fragment 20

References 18

[1]	Rao, C. B.; Anjaneyula, A. S. R.; Sarma, N. S.; Venkatateswarlu, Y.; Rosser, R. M.; Faulkner, D. J.; Chen, M. H.; Clardy, J. J. Am. Chem. Soc. 1984, 106, 7983.
[2]	Fukuzawa, S.; Hayashi, Y.; Uemura, D.; Nagatsu, A.; Yamada, K.; Ijuin, Y. Heterocycl. Commun. 1995, 1, 207.
[3]	Daranas, A. H.; Fernández, J.; Gavín, J.; Norte, M. Tetrahedron 1999, 55, 5539.
[4]	Cen-Pacheco, F.; Norte, M.; Fernández, J. J.; Daranas, A. H. Org. Lett. 2014, 16, 2880.
[5]	Cheng, Y.-B.; Lai, W.-C.; Tsai, Y.-C.; Wu, Y.-C.; Chang, F.-R. Tetrahedron Lett. 2014, 55, 5369.
[6]	(a) Tomanik, M.; Xu, Z.; Herzon, S. B. J. Am. Chem. Soc. 2021, 143, 699.
	(b) Tomanik, M.; Xu, Z.; Guo, F.; Wang, Z.; Yang, K. R.; Batista, V. S.; Herzon, S. B. J. Org. Chem. 2021, 86, 17011.
	(c) Shimakawa, T.; Nakamura, S.; Asai, H.; Hagiwara, K.; Inoue, M. J. Am. Chem. Soc. 2023, 145, 600.
	(d) Pan, Lu.; Schneider, F.; Ottenbruch, M.; Wiechert, R.; List, T.; Schoch, P.; Mertes, B.; Gaich, T. Nature 2024, 632, 543.
[7]	(a) Yamaguchi, K.; Yada, M.; Tsuji, T.; Kuramoto, M.; Uemura, D. Biol. Pharm. Bull. 1999, 22, 920.
	(b) Venkateswarlu, Y.; Reddy, N. S.; Ramesh, P.; Reddy, P. S.; Jsmil, K. Heterocycl. Commun. 1998, 4, 575.
	(c) Hirai, G.; Oguri, H.; Hayashi, M.; Koyama, K.; Koizumi, Y.; Moharram, S. M.; Hirama, M. Bioorg. Med. Chem. Lett. 2004, 14, 2647.
[8]	(a) Miyashita, M.; Sasaki, M.; Hattori, I.; Sakai, M.; Tanino, K. Science 2004, 305, 495.
	(b) Nielsen, T. E.; Tanner, D. J. Org. Chem. 2002, 67, 6366.
	(c) Juhl, M.; Monrad, R.; Søtofte, I.; Tanner, D. J. Org. Chem. 2007, 72, 4644.
	(d) Irifune, T.; Ohashi, T.; Ichino, T.; Sakia, E.; Suenaga, K.; Uemura, D. Chem. Lett. 2005, 34, 1058.
	(e) Williams, D. R.; Brugel, T. A. Org. Lett. 2000, 2, 1023.
	(f) Ling, T.; Kramer, B. A.; Palladino, M. A.; Theodorakis, E. A. Org. Lett. 2000, 2, 2073.
	(g) Ghosh, S.; Rivas, F.; Fischer, D.; GonzRlez, M. A.; Theodorakis, E. A. Org. Lett. 2004, 6, 941.
	(h) Hirai, G.; Koizumi, Y.; Moharram, S. M.; Oguri, H.; Hirama, M. Org. Lett. 2002, 4, 1627.
	(i) Behenna, D. C.; Stockdill, J. L.; Stoltz, B. M. Angew. Chem., Int. Ed. 2007, 46, 4077.
	(j) Yamashita, D.; Murata, Y.; Hikage, N.; Takao, K. I.; Nakazaki, A.; Kobayashi, S. Angew. Chem., Int. Ed. 2009, 48, 1404.
	(k) Xin, Z. Y.; Wang, H.; He, H. B.; Zhao, X. L.; Gao, S. H. Angew. Chem., Int. Ed. 2021, 60, 12807.
	(l) Chen, Y. Y.; Xin, Z. Y.; Wang, H.; He, H. B.; Gao, S. H. Org. Chem. Front. 2023, 10, 651.
[9]	(a) Shi, L.; Meyer, K.; Greaney, M. F. Angew. Chem., Int. Ed. 2010, 49, 9250.
	(b) Ma, B. J.; Zhao, Y. F.; He, C.; Ding, H. F. Angew. Chem., Int. Ed. 2018, 57, 1.
	(c) Cha, J. Y.; Yeoman, J. T. S.; Reisman, S. E. J. Am. Chem. Soc. 2011, 133, 14964.
	(d) Su, S. B.; Lin, C. C.; Zhai, H. B. Angew. Chem., Int. Ed. 2023, 62, e202303402.
	(d) Guo, L.; Tang, P. P. Chin. J. Org. Chem. 2021, 41, 3816. (in Chinese)
	(郭璐, 汤平平, 有机化学, 2021, 41, 3816.)
[10]	(a) Wipf, P.; Kim, Y. J. Org. Chem. 1993, 58, 1649.
	(b) Still, W. C. J. Am. Chem. Soc. 1978, 100, 1481.
	(c) Okamoto, R.; Takeda, K.; Tokuyama, H.; Ihara, M.; Toyota, M. J. Org. Chem. 2013, 78, 93.
[11]	(a) Yue, G. Z.; Yang, L.; Yuan, C. C.; Jiang, X. L.; Liu, B. Org. Lett. 2011, 13, 19, 5406.
	(b) Mohr, P. J.; Halcomb, R. L. J. Am. Chem. Soc. 2003, 125, 1712.
[12]	(a) Pace, V.; Castoldi, L.; Holzer, W. Adv. Synth. Catal. 2014, 356, 1761.
	(b) Miele, M.; Citarella, A.; Langer, T.; Urban, E.; Zehl, M.; Holzer, W.; Ielo, L.; Pace, V. Org. Lett. 2020, 22, 7629.
[13]	Tanemura, K.; Suzuki, S.; Horaguchi, T. J. Chem. Soc., Perkin Trans. 1 1992, 2997.
[14]	(a) Rivas, F.; Ghosh, S.; Theodorakis, E. A. Tetrahedron Lett. 2005, 46, 5281.
	(b) Wang, D.; Hou, M.; Ji, Y.; Gao, S.H. Org. Lett. 2017, 19, 1922.
[15]	Lifchits, O.; Mahlau, M.; Reisinger, C. M.; Lee, A.; Farès, C.; Polyak, I.; Gopakumar, G.; Thiel, W.; List, B. J. Am. Chem. Soc. 2013, 135, 6677.
[16]	Chow, K. Y. K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8126.
[17]	(a) Takamura, H.; Kikuchi, T.; Iwamoto, K.; Nakao, E.; Harada, N.; Otsu, T.; Endo, N.; Fukuda, Y. J.; Ohno, O.; Suenaga, K.; Guo, Y. W.; Kadota, I. J. Org. Chem. 2018, 83, 11028.
	(b) Prieto, J. A.; Torres, J. R.; Rodríguez-Berrios, R. Synlett 2014, 25, 433.
[18]	Yu, Q.; Yang, S.; Tang, C. Y.; Peng, L.; Zuo, Z. L.; Wang, L. L. Chin. J. Org. Chem. 2021, 41, 2820. (in Chinese)
	(于奇, 杨帅, 唐聪云, 彭林, 左之利, 汪亮亮, 有机化学, 2021, 41, 2820.)

Kuroshine类生物碱的合成研究

Synthetic Study of Kuroshine Alkaloids

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