Atroposelective Synthesis of Axial Biaryls by Dynamic Kinetic Resolution Using Engineered Imine Reductases
Xinyue Hao
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorZhuangfei Tian
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorZhouchang Yao
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Tienan Zang
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorShucheng Song
Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorProf. Liang Lin
Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorTianzhang Qiao
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14850 United States
Search for more papers by this authorCorresponding Author
Dr. Ling Huang
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorCorresponding Author
Prof. Haigen Fu
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorXinyue Hao
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorZhuangfei Tian
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorZhouchang Yao
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Tienan Zang
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorShucheng Song
Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorProf. Liang Lin
Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorTianzhang Qiao
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14850 United States
Search for more papers by this authorCorresponding Author
Dr. Ling Huang
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorCorresponding Author
Prof. Haigen Fu
NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 China
Search for more papers by this authorCorrection Statement September 16, 2024, Corrections have been made to the Legend for Figure 4 and a revised Supporting Information has been provided
Abstract
Axially chiral biaryl compounds are ubiquitous scaffolds in natural products, bioactive molecules, chiral ligands and catalysts, but biocatalytic methods for their asymmetric synthesis are limited. Herein, we report a highly efficient biocatalytic route for the atroposelective synthesis of biaryls by dynamic kinetic resolution (DKR). This DKR approach features a transient six-membered aza-acetal-bridge-promoted racemization followed by an imine reductase (IRED)-catalyzed stereoselective reduction to construct the axial chirality under ambient conditions. Directed evolution of an IRED from Streptomyces sp. GF3546 provided a variant (S-IRED-Ss-M11) capable of catalyzing the DKR process to access a variety of biaryl aminoalcohols in high yields and excellent enantioselectivities (up to 98 % yield and >99 : 1 enantiomeric ratio). Molecular dynamics simulation studies on the S-IRED-Ss-M11 variant revealed the origin of its improved activity and atroposelectivity. By exploiting the substrate promiscuity of IREDs and the power of directed evolution, our work further extends the biocatalysts’ toolbox to construct challenging axially chiral molecules.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
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References
- 1J. E. Smyth, N. M. Butler, P. A. Keller, Nat. Prod. Rep. 2015, 32, 1562–1583.
- 2S. R. Laplante, L. D. Fader, K. R. Fandrick, D. R. Fandrick, O. Hucke, R. Kemper, S. P. F. Miller, P. J. Edwards, J. Med. Chem. 2011, 54, 7005–7022.
- 3M. Basilaia, M. H. Chen, J. Secka, J. L. Gustafson, Acc. Chem. Res. 2022, 55, 2904–2919.
- 4M. Mccormick, J. Mcguire, G. Pittenger, R. Pittenger, W. Stark, Antibiot. Annu. 1955, 3, 606–611.
- 5S. M. Kupchan, R. W. Britton, M. F. Ziegler, C. J. Gilmore, R. J. Restivo, R. F. Bryan, J. Am. Chem. Soc. 1973, 95, 1335–1336.
- 6J. M. Brunel, Chem. Rev. 2005, 105, 857–898.
- 7Y.-D. Shao, D.-J. Cheng, ChemCatChem 2021, 13, 1271–1289.
- 8J. K. Cheng, S. H. Xiang, S. Li, L. Ye, B. Tan, Chem. Rev. 2021, 121, 4805–4902.
- 9J. Wencel-Delord, A. Panossian, F. R. Leroux, F. Colobert, Chem. Soc. Rev. 2015, 44, 3418–3430.
- 10P. Loxq, E. Manoury, R. Poli, E. Deydier, A. Labande, Coord. Chem. Rev. 2016, 308, 131–190.
- 11Z.-S. Liu, Y. Hua, Q. Gao, Y. Ma, H. Tang, Y. Shang, H.-G. Cheng, Q. Zhou, Nat. Catal. 2020, 3, 727–733.
- 12G. Liao, T. Zhou, Q.-J. Yao, B.-F. Shi, Chem. Commun. 2019, 55, 8514–8523.
- 13R. R. Surgenor, X. Liu, M. J. H. Keenlyside, W. Myers, M. D. Smith, Nat. Chem. 2023, 15, 357–365.
- 14J. Wu, M. C. Kozlowski, ACS Catal. 2022, 12, 6532–6549.
- 15A. Link, C. Sparr, Chem. Soc. Rev. 2018, 47, 3804–3815.
- 16K. Tanaka, Chem. – An Asian J. 2009, 4, 508–518.
- 17F. Guo, L. C. Konkol, R. J. Thomson, J. Am. Chem. Soc. 2011, 133, 18–20.
- 18J. A. Carmona, C. Rodríguez-Franco, R. Fernández, V. Hornillos, J. M. Lassaletta, Chem. Soc. Rev. 2021, 50, 2968–2983.
- 19C. B. Roos, C. H. Chiang, L. A. M. Murray, D. Yang, L. Schulert, A. R. H. Narayan, Chem. Rev. 2023, 123, 10641–10727.
- 20B. A. Lanman, A. T. Parsons, S. G. Zech, Acc. Chem. Res. 2022, 55, 2892–2903.
- 21R. Buller, S. Lutz, R. J. Kazlauskas, R. Snajdrova, J. C. Moore, U. T. Bornscheuer, Science 2024, 382, eadh8615.
- 22E. L. Bell, W. Finnigan, S. P. France, A. P. Green, M. A. Hayes, L. J. Hepworth, S. L. Lovelock, H. Niikura, S. Osuna, E. Romero, K. S. Ryan, N. J. Turner, S. L. Flitsch, Nat. Rev. Methods Primers. 2021, 1, 46.
- 23M. T. Reetz, G. Qu, Z. Sun, Nat. Synth. 2024, 3, 19–32.
- 24S. Wu, R. Snajdrova, J. C. Moore, K. Baldenius, U. T. Bornscheuer, Angew. Chem. Int. Ed. 2021, 60, 88–119.
- 25O. F. B. Watts, J. Berreur, B. S. L. Collins, J. Clayden, Acc. Chem. Res. 2022, 55, 3362–3375.
- 26B. Skrobo, J. D. Rolfes, J. Deska, Tetrahedron 2016, 72, 1257–1275.
- 27L. E. Zetzsche, J. A. Yazarians, S. Chakrabarty, M. E. Hinze, L. A. M. Murray, A. L. Lukowski, L. A. Joyce, A. R. H. Narayan, Nature 2022, 603, 79–85.
- 28H. Aldemir, R. Richarz, T. A. M. Gulder, Angew. Chem. Int. Ed. 2014, 53, 8286–8293.
- 29W. Hüttel, M. Müller, Nat. Prod. Rep. 2021, 38, 1011–1043.
- 30A. Chatterjee, H. Mallin, J. Klehr, J. Vallapurackal, A. D. Finke, L. Vera, M. Marsh, T. R. Ward, Chem. Sci. 2016, 7, 673–677.
- 31G. A. I. Moustafa, K. Kasama, K. Higashio, S. Akai, RSC Adv. 2019, 9, 1165–1175.
- 32K. Kasama, Y. Hinami, K. Mizuno, S. Horino, T. Nishio, C. Yuki, K. Kanomata, G. A. I. Moustafa, H. Gröger, S. Akai, Chem. Pharm. Bull. 2022, 70, 391–399.
- 33M. Ochiai, Y. Akisawa, D. Kajiyama, T. Matsumoto, Synlett 2019, 30, 557–562.
- 34K. Kasama, H. Aoyama, S. Akai, Eur. J. Org. Chem. 2020, 2020, 654–661.
- 35S. Staniland, B. Yuan, N. Giménez-Agullõ, T. Marcelli, S. C. Willies, D. M. Grainger, N. J. Turner, J. Clayden, Chem. A Eur. J. 2014, 20, 13084–13088.
- 36B. Yuan, A. Page, C. P. Worrall, F. Escalettes, S. C. Willies, J. J. W. McDouall, N. J. Turner, J. Clayden, Angew. Chem. Int. Ed. 2010, 49, 7010–7013.
- 37M. Ye, C. Li, D. Xiao, G. Qu, B. Yuan, Z. Sun, JACS Au 2024, 4, 411–418.
- 38G. A. I. Moustafa, Y. Oki, S. Akai, Angew. Chem. Int. Ed. 2018, 57, 10278–10282.
- 39S. Staniland, R. W. Adams, J. J. W. McDouall, I. Maffucci, A. Contini, D. M. Grainger, N. J. Turner, J. Clayden, Angew. Chem. Int. Ed. 2016, 55, 10755–10759.
- 40P. Rodríguez-Salamanca, G. de Gonzalo, J. A. Carmona, J. López-Serrano, J. Iglesias-Sigüenza, R. Fernández, J. M. Lassaletta, V. Hornillos, ACS Catal. 2023, 13, 659–664.
- 41J. M. Coto-Cid, G. de Gonzalo, J. A. Carmona, J. Iglesias-Sigüenza, P. Rodríguez-Salamanca, R. Fernández, V. Hornillos, J. M. Lassaletta, Adv. Synth. Catal. 2024, 366, 909–915.
- 42H. M. Snodgrass, D. Mondal, J. C. Lewis, J. Am. Chem. Soc. 2022, 144, 16676–16682.
- 43J. Mangas-Sanchez, S. P. France, S. L. Montgomery, G. A. Aleku, H. Man, M. Sharma, J. I. Ramsden, G. Grogan, N. J. Turner, Curr. Opin. Chem. Biol. 2017, 37, 19–25.
- 44B. Yuan, D. Yang, G. Qu, N. J. Turner, Z. Sun, Chem. Soc. Rev. 2024, 53, 227–262.
- 45A. K. Gilio, T. W. Thorpe, N. Turner, G. Grogan, Chem. Sci. 2022, 13, 4697–4713.
- 46X. Zhang, K. Zhao, Z. Gu, Acc. Chem. Res. 2022, 55, 1620–1633.
- 47Q. Shi, F. Fang, D.-J. Cheng, Adv. Synth. Catal. 2024, 366, 1269–1284.
- 48G. Bringmann, T. Hartung, Angew. Chem. Int. Ed. 1992, 31, 761–762.
- 49K. Mori, T. Itakura, T. Akiyama, Angew. Chem. Int. Ed. 2016, 55, 11642–11646.
- 50J. Zhang, J. Wang, Angew. Chem. Int. Ed. 2018, 57, 465–469.
- 51D. Guo, J. Zhang, B. Zhang, J. Wang, Org. Lett. 2018, 20, 6284–6288.
- 52S. P. France, G. A. Aleku, M. Sharma, J. Mangas-Sanchez, R. M. Howard, J. Steflik, R. Kumar, R. W. Adams, I. Slabu, R. Crook, G. Grogan, T. W. Wallace, N. J. Turner, Angew. Chem. Int. Ed. 2017, 56, 15589–15593.
- 53S.-W. Kang, D.-H. Ko, K. H. Kim, D.-C. Ha, Org. Lett. 2003, 5, 4517–4519.
- 54K. Mitsukura, M. Suzuki, K. Tada, T. Yoshida, T. Nagasawa, Org. Biomol. Chem. 2010, 8, 4533–4535.
- 55Y. Fukawa, K. Yoshida, S. Degura, K. Mitsukura, T. Yoshida, Chem. Commun. 2022, 58, 13222–13225.
- 56M. T. Reetz, J. D. Carballeira, Nat. Protoc. 2007, 2, 891–903.
- 57T. Huber, L. Schneider, A. Präg, S. Gerhardt, O. Einsle, M. Müller, ChemCatChem 2014, 6, 2248–2252.
- 58Deposition number CCDC 2353763 (for 8) contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallo-graphic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
- 59X. Bao, J. Rodriguez, D. Bonne, Angew. Chem. Int. Ed. 2020, 59, 12623–12634.
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