A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids

doi:10.6023/cjoc202204048

Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (9): 2857-2866.DOI: 10.6023/cjoc202204048 Previous Articles Next Articles

ARTICLES

印楝素类柠檬苦素化合物ABD核心骨架的快速合成

董长明^a, 谢熠^a, 梁广鑫^a^,^b^,^*()

a 南开大学化学学院元素有机化学国家重点实验室天津 300071
b 上海科技大学物质科学与技术学院上海201210

收稿日期:2022-04-18 修回日期:2022-05-31 发布日期:2022-06-16
通讯作者: 梁广鑫
基金资助:
国家重点研发计划(2017YFD0201404); 国家自然科学基金(21772097); 国家自然科学基金(21572104)

A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids

Changming Dong^a, Yi Xie^a, Guangxin Liang^a^,^b()

a State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
b School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210

Received:2022-04-18 Revised:2022-05-31 Published:2022-06-16
Contact: Guangxin Liang
Supported by:
National Key Research and Development Program of China(2017YFD0201404); National Natural Science Foundation of China(21772097); National Natural Science Foundation of China(21572104)

1. .pdf(3596KB)

Abstract

In an effort to rapidly construct the azadirachtin-type limonoids and analogues, a highly diastereoselective synthesis of the ABD tricyclic core in azadirachtin-type limonoids from (–)-carvone has been developed. The synthetic avenue features an intramolecular nitrile oxide-alkene cycloaddition (INOC) reaction to assemble the trans-decalin system in highly stereoselective manner. By further utilizing an efficient sequence of Sonogashira coupling, isoxazoline reduction, stereocontrolled dihydroxylation, mesylation and intramolecular S_N2 substitution, a scalable stereoselective synthesis of the tricyclic core skeleton of azadirachtin in 13 linear steps was achieved with 6.1% total yield. This intermediate can serve as a highly functionalized left-wing fragment for the synthesis of azadirachtin and its analogues. Compared with existing methods, the methods reported herein are simple, reliable, easy to implement, and significantly advances research on the synthesis of the azadirachtin-type limonoids.

Key words: azadirachtin, limonoids, trans-decalin, intramolecular nitrile oxide-alkene cycloaddition (INOC) reaction, isoxazoline

Cite this article

Changming Dong, Yi Xie, Guangxin Liang. A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids[J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2857-2866.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

Scheme 1. Selected syntheses of left-wing fragment of azadirachtin

Scheme 2. Retrosynthtic analysis of azadirachtin

Scheme 3. Construction of trans-decalin 2

Scheme 4. Construction of enol triflate tricyclic core

Scheme 5. Construction of alkyne tricyclic core

References 15

[1]	Schmutterer, H. The Neem Tree, Wiley-VCH, Weinheim, 1995.
[2]	(a) Buterworth, J. H.; Morgan, E. D. Chem. Commun. 1968, 35, 23.
	(b) Morgan, E. D. Bioorg. Med. Chem. 2009, 17, 4096. doi: 10.1016/j.bmc.2008.11.081
[3]	(a) Mordue (Luntz), A. J.; Simmonds, M. S. J.; Ley, S. V.; Blaney, W. M.; Mordue, W.; Nasiruddin, M.; Nisbet, A. J; . Pestic. Sci. 1998, 54, 277. doi: 10.1002/(SICI)1096-9063(1998110)54:3【-逻辑与-】#x00026;lt;277::AID-PS801【-逻辑与-】#x00026;gt;3.0.CO;2-I
	(b) Ley, S. V.; Denholm, A. A.; Wood, A. Nat. Prod. Rep. 1993, 10, 109. doi: 10.1039/np9931000109
[4]	Denholm, A. A.; Jennens, L.; Ley, S. V.; Wood, A. Tetrahedron 1995, 51, 6591. doi: 10.1016/0040-4020(95)00297-L
[5]	(a) Veitch, G. E.; Boyer, A.; Ley, S. V. Angew. Chem., Int. Ed. 2008, 47, 9402. doi: 10.1002/anie.200802675 pmid: 19031481
	(b) Veitch, G. E.; Beckmann, E.; Burke, B. J.; Boyer, A.; Maslen, S. L.; Ley, S. V. Angew. Chem., Int. Ed. 2007, 46, 7629. doi: 10.1002/anie.200703027 pmid: 19031481
	(c) Veitch, G. E.; Beckmann, E.; Burke, B. J.; Boyer, A.; Ayats, C.; Ley, S. V. Angew. Chem., Int. Ed. 2007, 46, 7633. doi: 10.1002/anie.200703028 pmid: 19031481
	(d) Ley, S. V.; Abad-Somovilla, A.; Anderson, J. C.; Ayats, C.; Bänteli, R.; Beckmann, E.; Boyer, A.; Brasca, M. G.; Brice, A.; Broughton, H. B.; Burke, B. J.; Cleator, E.; Craig, D.; Denholm, A. A.; Denton, R. M.; Durand-Reville, T.; Gobbi, L. B.; Göbel, M.; Gray, B. L.; Grossmann, R. B.; Gutteridge, C. E.; Hahn, N.; Harding, S. L.; Jennens, D. C.; Jennens, L.; Lovell, P. J.; Lovell, H. J.; de la Puente, M. L.; Kolb, H. C.; Koot, W.-J.; Maslen, S. L.; McCusker, C. F.; Mattes, A.; Pape, A. R.; Pinto, A.; Santafianos, D.; Scott, J. S.; Smith, S. C.; Somers, A. Q.; Spilling, C. D.; Stelzer, F.; Toogood, P. L.; Turner, R. M.; Veitch, G. E.; Wood, A.; Zumbrunn, C. Chem.-Eur. J. 2008, 14, 10683. doi: 10.1002/chem.200801103 pmid: 19031481
[6]	For studies towards the left-wing fragment by the Ley group, see: (a) Ley, S. V.; Lovell, P. J.; Slawin, A. M. Z.; Smith, S. C.; Williams, D. J.; Wood, A. Tetrahedron 1993, 49, 1675. doi: 10.1016/S0040-4020(01)80354-9
	(b) Kolb, H. C.; Ley, S. V. Tetrahedron Lett. 1991, 32, 6187. doi: 10.1016/0040-4039(91)80785-5
	(c) Kolb, H. C.; Ley, S. V.; Slawin, A. M. Z.; Williams, D. J. J. Chem. Soc., Perkin Trans. 1 1992, 2735.
	(d) Koot, W.-J.; Ley, S. V. Tetrahedron 1995, 51, 2077. doi: 10.1016/0040-4020(94)01071-7
	(e) Ley, S. V.; Lovell, P. J.; Smith, S. C.; Wood, A. Tetrahedron Lett. 1991, 32, 6183. doi: 10.1016/0040-4039(91)80784-4
[7]	(a) Kanoh, N.; Ishihara, J.; Murai, A. Synlett 1995, 895.
	(b) Yamamoto, Y.; Ishihara, J.; Kanoh, N.; Murai, A. Synthesis 2000, 1894.
	(c) Yamamoto, Y.; Ishihara, J.; Kanoh, N.; Murai, A. Synthesis 2000, 1894.
[8]	(a) Shi, H.; Tan, C. H.; Zhang, W. B.; Zhang, Z. C.; Long, R.; Gong, J. X.; Luo, T. P.; Yang, Z. J. Org. Chem. 2016, 81, 751. doi: 10.1021/acs.joc.5b02560
	(b) Shi, H.; Tan, C. H.; Zhang, W. B.; Zhang, Z. C.; Long, R.; Luo, T. P.; Yang, Z. Org. Lett. 2015, 17, 2342. doi: 10.1021/acs.orglett.5b00829
[9]	For other synthetic studies toward azadirachtin, see: Watanabe's work: (a) Mori, N.; Kitahara, T.; Mori, K.; Watanabe, H. Angew. Chem., Int. Ed. 2015, 54, 14920. doi: 10.1002/anie.201507935
	(b) Watanabe, H.; Watanabe, T.; Mori, K.; Kitahara, T. Tetrahedron Lett. 1997, 38, 4429. doi: 10.1016/S0040-4039(97)00923-4
	Tanino's, work:
	(c) Sakurai, K.; Tanino, K. Tetrahedron Lett. 2015, 56, 496. doi: 10.1016/j.tetlet.2014.12.062
	Nicolaou's, work:
	(d) Nicolaou, K. C.; Sasmal, P. K.; Koftis, T. V.; Converso, A.; Loizidou, E.; Kaiser, F.; Roecker, A. J.; Dellios, C. C.; Sun, X.-W.; Petrovic, G. Angew. Chem., Int. Ed. 2005, 44, 3447. doi: 10.1002/anie.200500217
	(e) Nicolaou, K. C.; Sasmal, P. K.; Roecker, A. J.; Sun, X.-W.; Mandal, S.; Converso, A. Angew. Chem., Int. Ed. 2005, 44, 3443. doi: 10.1002/anie.200500216
	(f) Nicolaou, K. C.; Roecker, A. J.; Monenschein, H.; Guntupalli, P.; Follmann, M. Angew. Chem., Int. Ed. 2003, 42, 3637. doi: 10.1002/anie.200351744
	(g) Nicolaou, K. C.; Follmann, M.; Roecker, A. J.; Hunt, K. W. Angew. Chem., Int. Ed. 2002, 41, 2103. doi: 10.1002/1521-3773(20020617)41:12【-逻辑与-】#x00026;lt;2103::AID-ANIE2103【-逻辑与-】#x00026;gt;3.0.CO;2-S
	(h) Nicolaou, K. C.; Roecker, A. J.; Follmann, M.; Baati, R. Angew. Chem., Int. Ed. 2002, 41, 2107. doi: 10.1002/1521-3773(20020617)41:12【-逻辑与-】#x00026;lt;2107::AID-ANIE2107【-逻辑与-】#x00026;gt;3.0.CO;2-4
[10]	Dong, C. M.; Qiao, T. J.; Xie, Y.; Zhang, X.; Ao, J. L.; Liang, G. X. Org. Chem. Front. 2020, 7, 1890. doi: 10.1039/D0QO00576B
[11]	(a) Kobayashi, K.; Kunimura, R.; Takagi, H.; Hirai, M.; Kogen, H.; Hirota, H.; Kuroda, C. J. Org. Chem. 2018, 83, 703. doi: 10.1021/acs.joc.7b02688 pmid: 29282987
	(b) Xuan, M.; Paterson, I.; Dalby, S. M. Org. Lett. 2012, 14, 5492. doi: 10.1021/ol302570k pmid: 29282987
[12]	Jiang, D. H.; Chen, Y. W. J. Org. Chem. 2008, 73, 9181. doi: 10.1021/jo801831c
[13]	Curran, D. P. J. Am. Chem. Soc. 1982, 104, 4024. doi: 10.1021/ja00378a050
[14]	Stepanov, A. V.; Veselovsky, V. V. Russ. Chem. Bull. 2002, 51, 359. doi: 10.1023/A:1015484416829
[15]	Baraldi, P. G.; Barco, A.; Benetti, S.; Manfredini, S.; Simoni, D. Synthesis 1987, 276.

印楝素类柠檬苦素化合物ABD核心骨架的快速合成

A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 15

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Haoran Liu, Junhao Yu, Tongyang Cao, Lin Qi, Lijing Wang. N-Iodosuccinimide-Promoted Cascade Oxoazidation of Alkenyl Oximes: Synthesis of Azido Isoxazolines [J]. Chinese Journal of Organic Chemistry, 2023, 43(12): 4220-4226.
[2]	Yunshu Liu, Guodong Zhao, Wenju Wu, Yunze Wang, Yanchao Yu, Jun You, Bo Liu. Study on Asymmetric Conjugate Cyanation of 3,5-Dimethyl-N-α,β-unsaturated Acylpyrazole Catalyzed by Magnesium-Bisoxazoline Complex [J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 208-217.
[3]	Liu Yingjie, Meng Jianping, Li Chen, Lin Liqing, Xu Ying. Progress in the Synthesis of Isoxazoline Derivatives by Cycloylation of Allyl Oxime [J]. Chinese Journal of Organic Chemistry, 2020, 40(9): 2742-2754.
[4]	Zhong Liangkun, Jiang Tao, Zhang Fan, Fu Qing, Liu Xinghai, Xu Tianming, Ding Chengrong, Chen Jie, Yuan Jing, Tan Chengxia. Synthesis and Insecticidal Activity of 3-Arylisoxazoline-pyrazole-5-carboxamide Derivatives [J]. Chin. J. Org. Chem., 2019, 39(9): 2655-2662.
[5]	Li Yongkun, Liu Bei, Zhang Lijun, Zhu Jiahong, Wan Chunping, Mao Zewei. Synthesis and Cytotoxic Activity of New 3-Aryl-5-furanyl-4, 5-dihydroisoxazoline Derivatives [J]. Chin. J. Org. Chem., 2018, 38(4): 949-954.
[6]	Li Minghui, Song Buer, Imerhasan Mukhtar. Progress in Synthesis and Bioactivity of Spiroisoxazoline Compounds [J]. Chin. J. Org. Chem., 2018, 38(2): 378-400.
[7]	Ning Guohui, Zhao Wentao, Bian Qiang, Tang Xiangyang. Synthesis and Fungicidal Activity of Some 3,5-Disubstituted Isoxazoline Derivatives [J]. Chin. J. Org. Chem., 2014, 34(9): 1800-1805.
[8]	Wei Baisong, Gu Wen, Xu Xu, Yang Yiqin, Wang Shifa. Synthesis and Antibacterial Activity of New Pinanyl Nitrogen-Containing Heterocycles [J]. Chin. J. Org. Chem., 2013, 33(10): 2196-2204.
[9]	Zhang Changshui, Ye Yong. Synthesis and Characterization of 5-phosphonyl 3-arylisoxazoline [J]. Chin. J. Org. Chem., 2012, 32(07): 1336-1339.
[10]	CHENG Chun-Sheng, YU Ping, LI Zhi-Nian, SU Jin-Yan, WANG Xin-Lei. 2-Methyl-3-(4-methoxyphenyl)-5-(3-methoxyphenyl)isoxazoline and Its Bioactivity [J]. Chin. J. Org. Chem., 2010, 30(06): 833-836.
[11]	Hu, Cui; Yang, Hongjun; Li, Ying; Yin, Shufan*. Synthesis and Calm Activity of 3-(4-β-D-Allopyranosyloxy-phenyl)-4- [(un)substituted anilinocarbonyl]-5-methoxycarbonyl-isoxazoline Derivatives [J]. Chin. J. Org. Chem., 2009, 29(01): 89-93.
[12]	Fan, Huidan^a ; Zhang, Conghai^a; Yan, Shengjiao^a ; Lin, Jun^*,a,b. Advances of Synthesis and Structure Modification and Bioactivity of Azadirachtin [J]. Chin. J. Org. Chem., 2009, 29(01): 20-33.
[13]	He, Xinwei ; Jin, Jie ; Wang, Cuie; Shang, Yongjia*. Synthesis of 2,5-Disubstituted Isoxazolines Using Poly(ethylene glycol) as Soluble Polymer Support [J]. Chin. J. Org. Chem., 2009, 29(01): 55-60.
[14]	ZHANG Jia-Ming,ZHANG Yong-Jian,ZHANG Wan-Bin*. Bisoxazoline Ligands with Chiral Backbones and Their Applications in Asymmetric Catalytic Reactions [J]. Chin. J. Org. Chem., 2007, 27(9): 1087-1095.
[15]	MA Lin-Ge,DU Da-Ming,XU Jia-Xi*. Effect of Chelate Size of Bisoxazolines on the Enantioselectivity of the Asymmetric Aziridination [J]. Chin. J. Org. Chem., 2006, 26(04): 568-572.