一种利用酰胺基转移反应脱除酰基保护基的实用方法

doi:10.6023/cjoc202112007

摘要/Abstract

酰胺化合物中的酰基脱除是有机合成化学的重要研究方向之一. 但是, 由于酰胺键较为惰性, 在温和条件下脱除酰基保护基的报道较少. 为了解决上述问题, 发展了一种使用氨水脱除酰基保护基的新方法. 该方法不但条件温和, 而且可以放大规模反应(10 mmol). 一系列药物分子或者药物分子衍生物, 例如吲哚美辛、N-乙酰基褪黑素及N-乙酰基卡布洛芬中的酰基都可以采用此方法高产率脱除. 该方法具有较好的官能团容忍性、操作简便、条件温和、产率高以及所用的试剂廉价易得等优势. 因此, 该方法有望成为N-酰基脱保护的实用方法之一.

关键词: 脱酰基, 酰胺基转移, 绿色合成, 酰胺

The N-deacylation of amides under mild conditions is highly desirable in organic synthesis, but it remains challenging due to the chemically robust nature of amide bond. A general solution to the N-deacylation of amides with NH₃•H₂O under mild and scalable conditions (10 mmol) was developed. A range of drugs and drug derivatives including indomethacin, N-acetyl melatonin and N-acetyl carprofen could be deacylated to release free amines in excellent yields. The good functional group compatibility, combined with operational simplicity, excellent yield and cost effectiveness of all reagents, makes this protocol a prime candidate for N-deacylation of amide.

Key words: deacylation, transamidation, green synthesis, amide

引用此文

韩群, 徐坤, 田发宁, 黄胜阳, 曾程初. 一种利用酰胺基转移反应脱除酰基保护基的实用方法[J]. 有机化学, 2022, 42(4): 1123-1128.

Qun Han, Kun Xu, Faning Tian, Shengyang Huang, Chengchu Zeng. A Practical Transamidation Strategy for the N-Deacylation of Amides[J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1123-1128.

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参考文献 30

[1]	(a) Wang, H.; Shi, J.; Tan, J.; Xu, W.; Zhang, S.; Xu, K. Org. Lett. 2019, 21, 9430. doi: 10.1021/acs.orglett.9b03641
	(b) Wang, X.; Xu, X.; Wang, Z.; Fang, P.; Mei, T. Chin. J. Org. Chem. 2020, 40, 3738. (in Chinese) doi: 10.6023/cjoc202003022
	( 王向阳, 徐学涛, 王振华, 方萍, 梅天胜, 有机化学, 2020, 40, 3738.) doi: 10.6023/cjoc202003022
	(c) Yang, Q.; Yan, X.-T.; Feng, C.-T.; Chen, D.-X.; Yan, Z.-Z.; Xu, K. Org. Chem. Front. 2021, 8, 6384. doi: 10.1039/D1QO01060C
	(d) Ge, Y.-X.; Yan, Q.-Q.; Tian, Y.-F.; Wang, H.-J.; Zhang, C.-F.; Li, Z.-J. Chin. J. Org. Chem. 2021, 41, 3106. (in Chinese) doi: 10.6023/cjoc202102035
	( 葛雅欣, 闫芹芹, 田云飞, 王海军, 张春芳, 李泽江, 有机化学, 2021, 41, 3106.) doi: 10.6023/cjoc202102035
	(e) Yi, R.-N.; He, W.-M. Chin. J. Org. Chem. 2021, 41, 1267. (in Chinese) doi: 10.6023/cjoc202100022
	( 易荣楠, 何卫民, 有机化学, 2021, 41, 1267.) doi: 10.6023/cjoc202100022
[2]	Baran, P. S.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 7904. pmid: 12095326
[3]	(a) Wen, J.; Wang, F.; Zhang, X. M. Chem. Soc. Rev. 2021, 50, 3211. doi: 10.1039/D0CS00082E
	(b) Jiang, X.-L.; Zhu, S.-L. Chin. J. Org. Chem. 2021, 41, 3745. (in Chinese) doi: 10.6023/cjoc202100068
	( 江晓莉, 朱少林, 有机化学, 2021, 41, 3745.) doi: 10.6023/cjoc202100068
[4]	(a) Zhang, M.; Zhang, Y.; Jie, X.; Zhao, H.; Li, G.; Su, W. P. Org. Chem. Front. 2014, 1, 843. doi: 10.1039/C4QO00068D
	(b) Luo, H.; Pei, N.; Zhang, J. Chin. J. Org. Chem. 2021, 41, 2990. (in Chinese) doi: 10.6023/cjoc202103013
	( 罗欢欢, 裴娜, 张敬, 有机化学, 2021, 41, 2990.) doi: 10.6023/cjoc202103013
	(c) Feng, Y.-L.; Shi, B. Chin. J. Org. Chem. 2021, 41, 3753. (in Chinese) doi: 10.6023/cjoc202104004
	( 冯亚岚, 史炳锋, 有机化学, 2021, 41, 3753.)
	(d) Sun, S.-Z.; Wang, X.; Cheng, T.-J.; Xu, H.; Dai, H.-X. Chin. J. Org. Chem. 2020, 40, 3371 (in Chinese) doi: 10.6023/cjoc202005064
	( 孙尚政, 王星, 程泰锦, 徐辉, 戴辉雄, 有机化学, 2020, 40, 3371.) doi: 10.6023/cjoc202005064
	(e) Liu, Y.-Y.; Zhang, Y.; Wan, J.-P. J. Org. Chem. 2017, 82, 8950. doi: 10.1021/acs.joc.7b01375
	(f) Du, Y.; Liu, Y.-Y.; Wan, J.-P. J. Org. Chem. 2018, 83, 3403. doi: 10.1021/acs.joc.8b00068
[5]	(a) Wuts, P. G. M.; Greene, T. W. Protective Groups in Organic Synthesis, 4th ed., Wiley-Interscience, Hoboken, 2006, pp. 773-789.
	(b) Yoo, M.; Jung, K.-W. ChemistrySelect 2018, 3, 1527. doi: 10.1002/slct.201702289
[6]	Spaggiari, A.; Blaszczak, L. C.; Prati, F. Org. Lett. 2004, 6, 3885. pmid: 15496055
[7]	Koenig, S. G.; Vandenbossche, C. P.; Zhao, H.; Mousaw, P.; Singh, S. P.; Bakale, R. P. Org. Lett. 2009, 11, 433. doi: 10.1021/ol802482d
[8]	Sultane, P. R.; Mete, T. B.; Bhat, R. G. Org. Biomol. Chem. 2014, 12, 261. doi: 10.1039/C3OB41971A
[9]	Wang, A.-E.; Chang, Z.; Liu, Y.-P.; Huang, P.-Q. Chin. Chem. Lett. 2015, 26, 1055. doi: 10.1016/j.cclet.2015.05.033
[10]	Kita, Y.; Nishii, Y.; Onoue, A.; Mashima, K. Adv. Synth. Catal. 2013, 355, 3391. doi: 10.1002/adsc.201300819
[11]	Shimizu, Y.; Morimoto, H.; Zhang, M.; Ohshima, T. Angew. Chem., Int. Ed. 2012, 51, 8564. doi: 10.1002/anie.201202354
[12]	(a) Lian, F.; Xu, K. Chin. J. Org. Chem. 2020, 40, 3490. (in Chinese) doi: 10.6023/cjoc202000072
	( 廉菲, 徐坤, 有机化学, 2020, 40, 3490.) doi: 10.6023/cjoc202000072
	(b) Meng, Z.-Y.; Feng, C.-T.; Xu, K. Chin. J. Org. Chem. 2021, 41, 2535. (in Chinese) doi: 10.6023/cjoc202012013
	( 蒙泽银, 冯承涛, 徐坤, 有机化学, 2021, 41, 2535.) doi: 10.6023/cjoc202012013
	(c) Lian, F.; Xu, K.; Zeng, C. Chem. Rec. 2021, 21, 2290. doi: 10.1002/tcr.202100036
	(d) Li, J.; Zhang, S.; Xu, K. Chin. Chem. Lett. 2021, 32, 2729. doi: 10.1016/j.cclet.2021.03.027
	(e) Zhang, S.; Li, L.; Li, J.; Shi, J.; Xu, K.; Gao, W.; Zong, L.; Li, G.; Findlater, M. Angew. Chem., Int. Ed. 2021, 60, 7275. doi: 10.1002/anie.202015230
	(f) Jiang, Y.; Xu, K.; Zeng, C. CCS Chem. 2021, 3, 1911.
[13]	Tordjman, S.; Chokron, S.; Delorme, R.; Charrier, A.; Bellissant, E.; Jaafari, N.; Fougerou, C. Curr. Neuropharmacol. 2017, 15, 434. doi: 10.2174/1570159X14666161228122115 pmid: 28503116
[14]	Wang, Y.-H.; Tian, J.-S.; Tan, P.-W.; Cao, Q.; Zhang, X.-X.; Cao, Z.-Y.; Zhou, F.; Wang, X.; Zhou, J. Angew Chem., Int. Ed. 2020, 59, 1634. doi: 10.1002/anie.201910864
[15]	Kerr, W. J.; Lindsay, D. M.; Owens, P. K.; Reid, M.; Tuttle, T.; Campos, S. ACS Catal. 2017, 7, 7182. doi: 10.1021/acscatal.7b02682
[16]	Roth, G. J.; Heckel, A.; Colbatzky, F.; Handschuh, S.; Kley, J.; Lintz, T. L.; Lotz, R.; Grunt, U. T.; Walter, R.; Hilberg, F. J. Med. Chem. 2009, 52, 4466. doi: 10.1021/jm900431g
[17]	Castelo-Branco, F. S.; Lima, E. C.; Domingos, J. L. O.; Pintob, A. C.; Lourenço, M. C. S.; Gomes, K. M.; Costa-Lima, M. M.; Araujo-Lima, C. F.; Aiub, C. A. F.; Felzenszwalb, I.; Costa, T. E. M. M.; Penido, C.; Henriques, M. G.; Boechat, N. Eur. J. Med. Chem. 2018, 146, 529. doi: S0223-5234(18)30084-9 pmid: 29407978
[18]	He, K.-H.; Tan, F.-F.; Zhou, C.-Z.; Zhou, G.-J.; Yang, X.-L.; Li, Y. Angew. Chem., Int. Ed. 2017, 56, 3080. doi: 10.1002/anie.201612486
[19]	Wang, Q.-F.; Chai, H.; Yu, Z.-K. Organometallics 2018, 37, 584. doi: 10.1021/acs.organomet.7b00902
[20]	Wu, J.-J.; Talwar, D.; Johnston, S.; Yan, M.; Xiao, J.-L. Angew. Chem., Int. Ed. 2013, 52, 6983.
[21]	Huang, Y.-Q.; Song, H.-J.; Liu, Y.-X.; Wang, Q.-M. Chem.-Eur. J. 2018, 24, 2065. doi: 10.1002/chem.201705202
[22]	Zhang, J.-Y.; Chen, S.-Y.; Chen, F.-F.; Xu, W.-S.; Deng, G.-J.; Gong, H. Adv. Synth. Catal. 2017, 359, 2358. doi: 10.1002/adsc.201700178
[23]	Ning, X.-S.; Liang, X.; Hu, K.-F.; Yao, C.-Z.; Qu, J.-P.; Kang, Y.-B. Adv. Synth. Catal. 2018, 360, 1590. doi: 10.1002/adsc.201701512
[24]	Barykina, O. V.; Snider, B. B. Org. Lett. 2010, 12, 2664. doi: 10.1021/ol100896n pmid: 20446668
[25]	Song, W. Z.; Dong, K.; Li, M. Org. Lett. 2020, 22, 371. doi: 10.1021/acs.orglett.9b03905
[26]	Wang, M.; Fan, Q.-L.; Jiang, X.-F. Org. Lett. 2018, 20, 216. doi: 10.1021/acs.orglett.7b03564
[27]	Omer, H. M.; Liu, P.; Brummond, K. M. J. Org. Chem. 2020, 85, 7959. doi: 10.1021/acs.joc.0c00788
[28]	Lin, W.; Hu, M.-H.; Feng, X.; Fu, L.; Cao, C.-P.; Huang, Z.-B.; Shi, D.-Q. Tetrahedron Lett. 2014, 55, 2238. doi: 10.1016/j.tetlet.2014.02.072
[29]	Laursen, S. R.; Jensen, M. T.; Lindhardt, A. T.; Jacobsen, M. F.; Skrydstrup, T. Eur. J. Org. Chem. 2016, 2016, 1881. doi: 10.1002/ejoc.201600143
[30]	Zhang, F.; Li, L.; Zhang, J. Sci. Rep. 2019, 9, 2787. doi: 10.1038/s41598-019-39240-z pmid: 30808919

Entry	Deviation from standard conditions	Yield/%
1	None	91
2	r.t.	68
3	60 ℃	90
4	DCM instead of MeOH	Trace
5	DCE instead of MeOH	Trace
6	THF instead of MeOH	Trace
7	MeCN instead of MeOH	47
8	EtOH instead of MeOH	67
9	1 mL MeOH	56
10	0.8 mL NH₃•H₂O	77
11	CH₃NH₂ instead of NH₃•H₂O	63

Entry	Deviation from standard conditions	Yield/%
1	None	91
2	r.t.	68
3	60 ℃	90
4	DCM instead of MeOH	Trace
5	DCE instead of MeOH	Trace
6	THF instead of MeOH	Trace
7	MeCN instead of MeOH	47
8	EtOH instead of MeOH	67
9	1 mL MeOH	56
10	0.8 mL NH₃•H₂O	77
11	CH₃NH₂ instead of NH₃•H₂O	63