苯乙烯及其衍生物的生物氨羟化反应用于β-氨基醇的高效合成

doi:10.1016/S1872-2067(22)64174-3

催化学报 ›› 2023, Vol. 44: 171-178.DOI: 10.1016/S1872-2067(22)64174-3

• 论文 • 上一篇

苯乙烯及其衍生物的生物氨羟化反应用于β-氨基醇的高效合成

胡瑞文^a^,¹, 龚安界^b^,¹, 廖浪星^b^,¹, 郑颜欣^b^,¹, 刘鑫^b, 吴鹏^b, 李福帅^b, 郁慧丽^a, 赵晶^a, 叶龙武^b^,^*(), 王斌举^b^,^*(), 李爱涛^a^,^*()

^a湖北大学生命科学学院, 工业生物技术湖北省重点实验室, 省部共建生物催化与酶工程国家重点实验室, 湖北武汉 430062
^b厦门大学化学化工学院, 理论与计算化学福建省重点实验室, 固体表面物理化学国家重点实验室, 福建厦门 360015

收稿日期:2022-07-23 接受日期:2022-09-21 出版日期:2023-01-18 发布日期:2022-12-08
通讯作者: 叶龙武,王斌举,李爱涛
作者简介:¹共同第一作者.
基金资助:
国家重点研发计划(2019YFA0906400);湖北省生物催化与酶工程技术引智创新示范基地项目(2019BJH021);省部共建生物催化与酶工程国家重点实验室自主研发项目

Biocatalytic aminohydroxylation of styrenes for efficient synthesis of enantiopure β-amino alcohols

Ruiwen Hu^a^,¹, Anjie Gong^b^,¹, Langxing Liao^b^,¹, Yan-Xin Zheng^b^,¹, Xin Liu^b, Peng Wu^b, Fushuai Li^b, Huili Yu^a, Jing Zhao^a, Long-Wu Ye^b^,^*(), Binju Wang^b^,^*(), Aitao Li^a^,^*()

^aState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of life science, Hubei University, Wuhan 430062, Hubei, China
^bState Key Laboratory of Physical Chemistry of Solid Sur-faces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 360015, Fujian, China

Received:2022-07-23 Accepted:2022-09-21 Online:2023-01-18 Published:2022-12-08
Contact: Long-Wu Ye, Binju Wang, Aitao Li
About author:¹ Contributed equally to this work.
Supported by:
National Key Research and Development Program of China(2019YFA0906400);Innovation Base for Introducing Talents of Discipline of Hubei Province(2019BJH021);Research Program of State Key Laboratory of Biocatalysis and Enzyme Engineering

摘要/Abstract

摘要：

β-氨基醇是非常重要的手性砌块, 广泛用于药物、天然产物、氨基酸及其手性助剂的合成. 迄今为止, 超过300000种含有此类结构单元的化合物已被报道, 其中包括2000多种天然产物、80多种已获批准的药物以及超过100种候选药物. 鉴于β-氨基醇的重要作用, 对映选择性高效合成β-氨基醇具有非常重大的意义. 过去几十年, 研究人员一直致力于β-氨基醇高效合成方法的开发. 其中, 通过利用过量的胺作为胺供体直接与环氧化物进行氨解反应, 是合成β-氨基醇最为实用和认可的方法之一. 此外, 科学家也开发了使用各种路易斯酸或在不同有机溶剂中反应的化学法来提高环氧化物氨解反应的效率. 然而, 这些方法普遍存在反应温度高、催化剂用量大、催化剂对水敏感以及有机溶剂危害大等缺陷. 为了解决这些问题, 研究人员进一步开发出了水溶液体系中不依赖催化剂的环氧化物氨解反应, 用于氨基醇高效合成. 但该方法仍然需要以高反应活性的环氧化物作为起始原料, 导致其在选择性控制和后期应用方面存在一定的问题. 此外, 环氧化物(尤其是手性环氧化物)难以制备, 通常需要金属催化剂在苛刻的反应条件下进行. 相比之下, 以廉价易得的烯烃作为底物, 通过Sharpless不对称胺羟化反应合成氨基醇是一种极具潜力的方法, 但该方法对许多类型烯烃如末端烯烃的催化活性很低.

针对上述问题, 本文发展了一种酶法催化烯烃不对称氨羟化反应, 采用一锅法合成光学纯的β-氨基醇, 它以血红素依赖性细胞色素P450单加氧酶或黄素(FAD)依赖性苯乙烯单加氧酶作为催化剂. 首先, 催化烯烃不对称环氧化生产手性环氧化物中间体, 然后利用苯胺作为胺供体与环氧化物发生自发的化学氨解反应, 从而合成相应光学纯的β-氨基醇. 利用cluster-continuum(HCC)模型计算结合实验研究了环氧化物中间体与苯胺的氨解机理以及水分子在该反应中的关键作用. 结果表明, 产物β-氨基酸的光学纯度是由酶促反应中形成的环氧化物的绝对构型所决定. 基于此, 本文发掘了具有不同立体选择性的P450单加氧酶或苯乙烯单加氧酶, 用于催化苯乙烯和苯胺的氨羟化反应, 并对反应条件, 包括底物浓度、胺供体浓度以及底物添加方式进行优化, 分别高效地合成了(S)-和(R)-构型的两种氨基醇, 得率均为90%, 产物的ee值分别为90%和99%. 最后, 对该生物催化体系进行了底物谱的拓展, 用于催化苯乙烯及其衍生物与苯胺的分子间的氨羟化反应, 实现了多种相应(R)-或(S)-构型β-氨基醇的高效合成, 得率为87%‒97%, ee值为90%‒99%. 综上, 本文开发的人工生物催化体系, 为光学纯的β-氨基醇的高效合成提供了一种高效、绿色环保的新策略.

关键词: 氨羟化反应, β-氨基醇, 烯烃单加氧酶, 环氧化物氨解, 化学酶反应

Abstract:

A general biocatalytic process of intermolecular aminohydroxylation of styrenes with aniline has been achieved for efficient one-pot preparation of enantiopure β-amino alcohols. The reaction involves first asymmetric epoxidation of alkene substrates by a heme-dependent monooxygenase (P450) or the FAD-dependent styrene monooxygenase, followed by the aminolysis of nascent epoxide intermediates with aniline in water solution. Hybrid cluster-continuum (HCC) model calculations reveal the mechanism of the aminolysis of epoxide with aniline as well as the critical role of the water in mediating such a reaction. In addition, the combined experiments with simulations demonstrate that the chirality of amino alcohol is determined by the absolute configuration of the epoxide formed in the enzymatic reaction. In conclusion, the developed biocatalytic process provides an efficient, environmentally friendly approach for production of high value-added enantiopure β-amino alcohols, starting from cheap and readily available alkenes.

Key words: Aminohydroxylation, β-amino alcohols, Alkene monooxygenase, Aminolysis of epoxide, Chemoenzymatic reaction

胡瑞文, 龚安界, 廖浪星, 郑颜欣, 刘鑫, 吴鹏, 李福帅, 郁慧丽, 赵晶, 叶龙武, 王斌举, 李爱涛. 苯乙烯及其衍生物的生物氨羟化反应用于β-氨基醇的高效合成[J]. 催化学报, 2023, 44: 171-178.

Ruiwen Hu, Anjie Gong, Langxing Liao, Yan-Xin Zheng, Xin Liu, Peng Wu, Fushuai Li, Huili Yu, Jing Zhao, Long-Wu Ye, Binju Wang, Aitao Li. Biocatalytic aminohydroxylation of styrenes for efficient synthesis of enantiopure β-amino alcohols[J]. Chinese Journal of Catalysis, 2023, 44: 171-178.

×
扫码分享

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.cjcatal.com/CN/10.1016/S1872-2067(22)64174-3

https://www.cjcatal.com/CN/Y2023/V44/I1/171

图/表 5

Fig. 1. Traditional chemical and proposed biocatalytic approaches for the production of β-amino alcohols. (a) Current process for β-amino alcohols synthesis by multistage chemical methods, including first asymmetric epoxidation with Jacobsen metal catalysts, followed by aminolysis of epoxides with an excess amine in presence of a Lewis acid or different organic solvents. (b) Proposed one-pot biocatalytic method for β-amino alcohols synthesis with an alkene monooxygenase as catalyst and the thereby generated epoxide serving as an intermediate.

Fig. 2. The asymmetric intermolecular aminohydroxylation of styrene 1a with aniline 1b to produce β-amino alcohols 1c and 1d by using P450-BM3 WT as catalyst. Reaction conditions: cell suspension in phosphate buffer (OD600 ≈ 40, pH = 8.5, 200 mmol/L), 2 mmol/L 1a and 2 mmol/L 1b, DMSO (2% v/v), 25 °C, 220 r/min; the cofactor NADPH is provided by the E. coli host cells using 25 mmol/L glucose as an energy source.

Fig. 3. Gibbs energy profile (in kcal/mol) for the addition of aniline to (S)-styrene oxide. Alongside the energy profile are shown the schematic drawings and optimized structures of key species. The optimized structures of key species involved in reactions are shown below.

Fig. 4. The P450-BM3 F87G and styrene monooxygenase styAB catalyzed intermolecular aminohydroxylation of styrene with aniline to produce the corresponding β-amino alcohols. (a) Time course of recombinant E. coli (P450-BM3 F87G) catalyzed asymmetric intermolecular aminohydroxylation of styrene with aniline for the production of (S)-1c in a one-pot two-step approach. (b) Time course of recombinant E. coli (styAB) catalyzed asymmetric intermolecular aminohydroxylation of styrene with aniline for the production of (R)-1c in a one-pot two-step approach. Reaction conditions: recombinant E. coli cells expressing P450-BM3 F87G or styAB were resuspended in phosphate buffer (pH = 8.5, 200 mmol/L) at a cell density of OD600 ≈ 40, styrene (5 mmol/L) was first added and reacted for 1 h, followed by addition of aniline (30 mmol/L) for another 23 h reaction; reactions were performed at 25 °C, 220 r/min with cofactor NADPH provided by the E. coli host cells using 25 mmol/L glucose as an energy source.

Table 1 Asymmetric intermolecular aminohydroxylation of para-styrenes 1a?4a with aniline to produce the corresponding enantiopure β-amino alcohols 1c?4c catalyzed by E. coli (P450-BM3 F87G), E. coli (P450pyrTM) or E. coli (styAB) a.

Entry	Sub.	Enzymes	Prod.	Yiled^b (%)	ee ^c (%)
1	1a	P450-BM3 F87G	(S)-1c	90	90
2	1a	styAB	(R)-1c	90	99
3	2a	P450pyrTM	(S)-2c	93	99
4	3a	P450pyrTM	(S)-3c	87	90
5	2a	styAB	(R)-2c	92	99
6	3a	styAB	(R)-3c	86	99
7	4a	styAB	(R)-4c	97	95

参考文献

[1]	J. K. Ekegren, N. Ginman, A. Johansson, H. Wallberg, M. Larhed, B. Samuelsson, T. Unge, A. Hallberg, J. Med. Chem., 2006, 49, 1828-1832.
[2]	M. Sato, H. Kawakami, T. Motomura, H. Aramaki, T. Matsuda, M. Yamashita, Y. Ito, Y. Matsuzaki, K. Yamataka, S. Ikeda, H. Shinkai, J. Med. Chem., 2009, 52, 4869-4882.
[3]	S. C. Bergmeier, Tetrahedron, 2000, 56, 2561-2576.
[4]	D. C. Blakemore, L. Castro, I. Churcher, D. C. Rees, A. W. Thomas, D. M. Wilson, A. Wood, Nat. Chem., 2018, 10, 383-394.
[5]	D. J. Ager, I. Prakash, D. R. Schaad, Chem. Rev., 1996, 96, 835-876.
[6]	E. J. Corey, F. Zhang, Angew. Chem. Int. Ed., 1999, 38, 1931-1934.
[7]	C. W. Johannes, M. S. Visser, G. S. Weatherhead, A. H. Hoveyda, J. Am. Chem. Soc., 1998, 120, 8340-8347.
[8]	M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Keßeler, R,. Stürmer, T. Zelinski, Angew. Chem. Int. Ed., 2004, 43, 788-824.
[9]	T. Sehl, Z. Maugeri, D. Rother, J. Mol. Catal. B, 2015, 114, 65-71.
[10]	D. Ghislieri, N. J. Turner, Top. Catal., 2014, 57, 284-300.
[11]	O. K. Karjalainen, A. M. P. Koskinen, Org. Biomol. Chem., 2012, 10, 4311-4326.
[12]	S. C. Bergmeier, Tetrahedron, 2000, 56, 2561-2576.
[13]	F.-F. Chen, S. C. Cosgrove, W. R. Birmingham, J. Mangas-Sanchez, J. Citoler, M. P. Thompson, G.-W. Zheng, J.-H. Xu, N. J. Turner, ACS Catal., 2019, 9, 11813-11818.
[14]	C.-X. Ye, Y. Y. Melcamu, H.-H. Li, J.-T. Cheng, T.-T. Zhang, Y.-P. Ruan, X. Zheng, X. Lu, P.-Q. Huang, Nat. Commun., 2018, 9, 410.
[15]	K. M. Nakafuku, Z. Zhang, E. A. Wappes, L. M. Stateman, A. D. Chen, D. A. Nagib, Nat. Chem., 2020, 12, 697-704.
[16]	M. Zhu, Q. Zhang, W. Zi, Angew. Chem. Int. Ed., 2021, 60, 6545-6552.
[17]	B. Liu, P. Xie, J. Zhao, J. Wang, M. Wang, Y. Jiang, J. Chang, X. Li, Angew. Chem. Int. Ed., 2021, 60, 8396-8400.
[18]	L. Jia, X. Wang, X. Gao, M. Makha, X.-C. Wang, Y. Li, Green Synth. Catal., 2022, 3, 259-264.
[19]	D. M. Hodgson, A. R. Gibbs, G. P. Lee, Tetrahedron, 1996, 52, 14361-14384.
[20]	R. M. Hanson, Chem. Rev., 1991, 91, 437-475.
[21]	Y. Yamamoto, N. Asao, M. Meguro, N. Tsukade, H. Nemoto, N. Adayari, J. G. Wilson, H. Nakamura, J. Chem. Soc., Chem. Commun., 1993, 1201-1203.
[22]	K. Surendra, N. S. Krishnaveni, K. R. Rao, Synlett, 2005, 506-510.
[23]	M. M. Mojtahedi, M. R. Saidi, M. Bolourtchian, J. Chem. Res., 1999, 128-129.
[24]	U. Das, B. Crousse, V. Kesavan, D. Bonnet-Delpon, J.-P. Begue, J. Org. Chem., 2000, 65, 6749-6751.
[25]	J. S. Yadav, B. V. S. Reddy, A. K. Basak, A. V. Narsaiah, Tetrahedron Lett., 2003, 44, 1047-1050.
[26]	T. Ollevier, G. Lavie-Compin, Tetrahedron Lett., 2004, 45, 49-52.
[27]	A. K. Chakraborti, A. Kondaskar, Tetrahedron Lett., 2003, 44, 8315-8319.
[28]	N. Azizi, M. R. Saidi, Org. Lett., 2005, 7, 3649-3651.
[29]	W. Zhang, J. L. Loebach, S. R. Wilson, E. N. Jacobsen, J. Am. Chem. Soc., 1990, 112, 2801-2803.
[30]	N. S. Barta, D. R. Sidler, K. B. Somerville, S. A. Weissman, R. D. Larsen, P. J. Reider, Org. Lett., 2000, 2, 2821-2824.
[31]	M. M. Heravi, T. B. Lashaki, B. Fattahi, V. Zadsirjan, RSC Adv., 2018, 8, 6634-6659.
[32]	P. Quinodoz, B. Drouillat, K. Wright, J. Marrot, F. Couty, J. Org. Chem., 2016, 81, 2899-2910.
[33]	M. M. Vaidergorn, Z. A. Carneiro, C. D. Lopes, S. de Albuquerque, F. C. Reis, S. Nikolaou, J. F. Mello, G. Genesi, G. H. Trossini, A. Ganesan, F. S. Emery, Eur. J. Med. Chem., 2018, 157, 657-664.
[34]	Li J,. Liu S. Q., Pham Z. Li, Chem. Commun., 2013, 49, 11572-11574.
[35]	H. Zhou, B. Wang, F. Wang, X. Yu, L. Ma, A. Li, M. T. Reetz, Angew. Chem. Int. Ed., 2019, 58, 764-768.
[36]	M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, Williams, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell,J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E. N. Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman, D. J. Fox, Gaussian 16, Rev. A.03, Wallingford, CT, 2016.
[37]	A. V. Marenich, C. J. Cramer, D. G. Truhlar, J. Phys. Chem. B, 2009, 113, 6378-6396.
[38]	C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B, 1988, 37, 785-789.
[39]	A. D. Becke, J. Chem. Phys., 1992, 97, 9173-9177.
[40]	A. D. Becke, J. Chem. Phys., 1993, 98, 5648-5652.
[41]	S. Grimme, J. Comput. Chem., 2006, 27, 1787-1799.
[42]	S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys., 2010, 132, 154104.
[43]	S. Grimme, S. Ehrlich, L. Goerigk, J. Comput. Chem., 2011, 32, 1456-1465.
[44]	K. L. Tee, U. Schwaneberg, Angew. Chem. Int. Ed., 2006, 45, 5380-5383.
[45]	A. Li, J. Liu, S. Q. Pham, Z. Li, Chem. Commun., 2013, 49, 11572-11574.
[46]	S. Panke, B. Witholt, A. Schmid, M. G. Wubbolts, Appl. Environ. Microbiol., 1998, 64, 2032-2043.
[47]	X. Zhang, Y. Peng, J. Zhao, Q. Li, X. Yu, C. G. Acevedo-Rocha, A. Li, Bioresour. Bioprocess., 2020, 7, 2.
[48]	S. Kille, F. E. Zilly, J. P. Acevedo, M. T. Reetz, Nat. Chem., 2011, 3, 738-743.
[49]	R. J. Li, Z. Zhang, C. G. Acevedo-Rocha, J. Zhao, A. Li, Green Synth. Catal., 2020, 1, 52-59.
[50]	Y. Li, B. Yuan, Z. Sun, W. Zhang, Green Synth. Catal., 2021, 2, 267-274.
[51]	C. J. C. Whitehouse, S. G. Bella, L.-L. Wong, Chem. Soc. Rev., 2012, 41, 1218-1260.
[52]	J. R. Pliego, J. M. Riveros, J. Phys. Chem. A, 2001, 105, 7241-7247.
[53]	B. Wang, Z. Cao, J. Phys. Chem. A, 2010, 114, 12918-12927.
[54]	H. Zhou, B. Wang, F. Wang, X. Yu, L. Ma, A. Li, M. T. Reetz, Angew. Chem. Int. Ed., 2019, 58, 764-768.
[55]	W. Zhang, W. L. Tang, Z. Wang, Z. Li, Adv. Synth. Catal., 2010, 352, 3380-3390.
[56]	G. Qu, A. Li, C. G. Acevedo-Rocha, Z. Sun, M. T. Reetz, Angew. Chem. Int. Ed., 2020, 59, 13204-13231.

苯乙烯及其衍生物的生物氨羟化反应用于β-氨基醇的高效合成

Biocatalytic aminohydroxylation of styrenes for efficient synthesis of enantiopure β-amino alcohols

RichHTML

PDF

Supporting Information

可视化

摘要/Abstract

引用本文

使用本文

扫码分享

图/表 5

参考文献

相关文章 0

编辑推荐

Metrics