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DOI: https://doi.org/10.6023/A26050176

Article

Asymmetric Reduction of Fluorinated Aromatic Ketones Mediated by Daucus carota and Coriandrum sativum

  • Yun-Hao Tang ,
  • Qi-Zhi Zhou ,
  • Tao Wang ,
  • Zhi-Heng Qiu ,
  • Xiao-Jing Le ,
  • Yan Zhang ,
  • Jin-Sheng Yu
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  • aShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062;
    bJunior Middle School of No.2 High School Affiliated to East China Normal University, Shanghai 200241

Received date: 2026-05-26

  Online published: 2026-07-10

Supported by

Technology Innovation Project of Shanghai Municipal Agricultural Committee (No. HNK(T2023302)) and the National Natural Science Foundation of China (No. 22471073).

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Abstract

Fluorinated chiral secondary alcohols represent a prominent structural motif in many pharmaceuticals, agrochemicals, and bioactive molecules. The development of green, efficient, and highly enantioselective synthetic methods for the facile access of such motifs is of great significance. Plant whole-cell biocatalysis has recently emerged as an ideal and sustainable strategy for the asymmetric reduction of ketones to afford chiral secondary alcohols. This environment benign approach offers several advantages, including low-cost and readily available catalysts, mild reaction conditions, and no need for enzyme isolation or purification. However, the preparation of fluorinated chiral secondary alcohols using this method remains largely underdeveloped. In this study, we investigated the asymmetric reduction of fluorinated aromatic ketones using inexpensive and readily available plant tissues as whole-cell biocatalysts. Through systematic optimization of reaction parameters-including plant source, pH, substrate concentration, biocatalyst loading, and temperature-the Sanhong carrot (Daucus carota subsp. sativus) was found to exhibit excellent enantioselectivity in the reduction of fluorinated aromatic ketones, affording 11 fluorinated chiral secondary alcohols in moderate to good yields (21-85%) and moderate to excellent enantioselectivities (59->99% ee). These products include several key intermediates for the synthesis of drugs and agrochemical molecules. Furthermore, a gram-scale synthesis of (S)-1-(3-trifluoromethylphenyl)ethanol—a key intermediate for accessing (S)-MA20565, which possesses broad-spectrum antifungal activity—was successfully accomplished. Starting from 1.0 g of 3′-(trifluoromethyl)acetophenone 1a, the desired product (S)-2a was obtained in 0.766 g (76% yield) with >99% ee. Notably, this study discloses for the first time that coriander roots (Coriandrum sativum) can serve as whole-cell biocatalysts for the highly selective reduction of fluorinated ketones, delivering the corresponding products in 10-71% yields and 47->99% ee. For certain substrates, coriander roots even outperformed carrots, providing a novel biocatalyst resource for asymmetric synthesis via plant whole-cell catalysis. Thus, it provides a new strategy for the green and highly enantioselective synthesis of fluorinated chiral secondary alcohols.

Key words： Fluorinated chiral secondary alcohols; Whole-cell biocatalysis; Asymmetric reduction; Daucus carota subsp. Sativus; Coriandrum sativum

Cite this article

Yun-Hao Tang , Qi-Zhi Zhou , Tao Wang , Zhi-Heng Qiu , Xiao-Jing Le , Yan Zhang , Jin-Sheng Yu . Asymmetric Reduction of Fluorinated Aromatic Ketones Mediated by Daucus carota and Coriandrum sativum[J]. Acta Chimica Sinica, 0 : 3 -3 . DOI: 10.6023/A26050176

References

[1] (a) Cotman A. E., Dub P. A., Sterle, M., Lozinšek, M., Dernovšek, J., Zajec, Z., Zega, A., Tomašič, T., Cahard D. ACS Org. Inorg. Au. 2022, 2, 396.
(b) Zheng, K., Lin, L. L., Feng, X. M. Acta Chim. Sinica. 2012, 70, 1785 (in Chinese).
(郑柯，林丽丽，冯小明，化学学报，2012, 70, 1785.).
(c) Burchell-Reyes, K., Paquin, J. F. Org. Biomol. Chem. 2025, 23, 4593.
[2] (a) Zhao, M. M., McNamara, J. M., Ho, G. J., Emerson, K. M., Song, Z. J., Tschaen, D. M., Brands, K. M. J., Dolling, U. H., Grabowski, E. J. J., Reider, P. J., Cottrell, I. F., Ashwood, M. S., Bishop, B. C. J. Org. Chem. 2002, 67, 6743.
(b) Brands, K. M. J., Payack, J. F., Rosen, J. D., Nelson, T. D., Candelario, A., Huffman, M. A., Zhao, M. M., Li, J., Craig, B., Song, Z. J., Tschaen, D. M., Hansen, K., Devine, P. N., Pye, P. J., Rossen, K., Dormer, P. G., Reamer, R. A., Welch, C. J., Mathre, D. J., Tsou, N. N., McNamara, J. M., Reider, P. J. J. Am. Chem. Soc. 2003, 125, 2129.
(c) Wang, L., Xu, G., Yang, L. R. Chem. Ind. Eng. Prog. 2013, 32, 2691 (in Chinese).
(王亮，徐刚，杨立荣，化工进展，2013, 32, 2691.)
[3] (a) Chinkov, N., Warm, A., Carreira, E. M. Angew. Chem. Int. Ed. 2011, 50, 2957.
(b) Okusu, S., Hirano, K., Yasuda, Y., Tanaka, J., Tokunaga, E., Fukaya, H., Shibata, N. Org. Lett. 2016, 18, 5568.
(c) Bastos, M. M., Costa, C. C. P., Bezerra, T. C., da Silva, F. d. C., Boechat, N. Eur. J. Med. Chem. 2016, 108, 455.
[4] (a) Hua, Y. Y., Bin, H. Y., Wei, T., Cheng, H. A., Lin, Z. P., Fu, X. F., Li, Y. Q., Xie, J. H., Yan, P. C., Zhou, Q. L. Org. Lett. 2020, 22, 818.
(b) Chung, J. Y. L., Scott, J. P., Anderson, C., Bishop, B., Bremeyer, N., Cao, Y., Chen, Q. H, Dunn, R., Kassim, A., Lieberman, D., Aaron, J., Moment, F. S., Zacuto, M. Org. Process Res. Dev. 2015, 19, 1760.
[5] (a) Tanaka, K., Katsurada, M., Ohno, F., Shiga, Y., Oda, M. J. Org. Chem. 2000, 65, 433.
(b) Jiang, X. L., Prasad, K., Repič, O. Synth. Commun. 2009, 39, 2640.
[6] (a) Hird, M. Chem. Soc. Rev. 2007, 36, 2070.
(b) Wang, Z. H., Han, W. Q., Shi, R., Han, X., Zheng, Y. S., Xu, J. L., Bu, X. H. JACS Au, 2024, 4, 279.
(c) Dai, S. T., Zhong, J. B., Yang, X. Q., Chen, C., Zhou, L. P., Liu, X. Y., Sun, J. B., Ye, K. Q., Zhang, H. Y., Li, L., Naumov, P., Lu, R. Angew. Chem. Int. Ed. 2024, 63, e202320223.
[7] (a) Wang, J., Sánchez-Roselló, M., Aceña, J. L., del Pozo, C., Sorochinsky, A. E., Fustero, S., Soloshonok, V. A., Liu, H. Chem. Rev. 2014, 114, 2432.
(b) Tan, X. F., Zeng, W. J., Wen, J. L., Zhang, X. M. Org. Lett., 2020, 22, 7230.
(c) Wu, Y. H., Wang, K. J., Wu, X., Wu, J. J., Wu, F. H. Org. Biomol. Chem. 2023, 21, 3623.
[8] (a) Yang, S. Y., Sun, C. K., Lin, X. F., Ma, S. Y., Li, Z. H. Acta Chim. Sinica. 2003, 61, 192 (in Chinese).
(杨思娅，孙成科，林雪飞，马思渝，李宗和，化学学报，2003, 61, 192.)
(b) Brüning, F., Nagae, H., Käch, D., Mashima, K., Togni, A. Chem. Eur. J. 2019, 25, 10818.
(c) Tan, X. F., Zeng, W. J., Wen, J. L., Zhang, X. M. Org. Lett. 2020, 22, 7230.
(d) Bacheley, L., Guillamot, G., Phansavath, P., Ratovelomanana-Vidal, V. Tetrahedron, 2024, 152, 133781.
(e) Li, B., Zhang, J. F., Nie, H. F., Lu, Z. X., Yang, G. D., Zhang, S. Y. Acta Chim. Sinica. 2025, 83, 661 (in Chinese).
(李斌，张静枫，聂慧芳，卢泽星，杨贵东，张生勇，化学学报，2025, 83, 661.)
[9] (a) Kawanami, Y., Hoshino, K., Tsunoi, W. Tetrahedron: Asymmetry, 2011, 22, 1464.
(b) Ren, X. Y, Li, G., Wei, S., Du, H. F. Org. Lett. 2015, 17, 990.
(c) Kawanami, Y., Yanagita, R. C. Molecules, 2018, 23, 2408.
[10] (a) Carvalho, C. C. C. R. D. Biotechnol. Adv. 2011, 29, 75.
(b) Hoff, B. H., Sund, E. Bioorg. Chem., 2013, 51, 31.
(c) Wu, Y. H., Wang, K. J., Wang, X., Wu, J. J., Wu, F. H. Org. Biomol. Chem. 2023, 21, 3623.
[11] (a) Bacheley, L., Guillamot, G., Phansavath, P., Ratovelomanana Vidal, V. Tetrahedron, 2024, 152, 133781.
(b) Fan, L. X., Zhao, X. H., Chen, X. Y., Shen, F. Y., Feng, W. Q., Feng, K., Ling, F., Zhong, W. H. Org. Lett. 2026, 28, 4531.
[12] (a) Yang, Z. H., Zeng, R., Yang, G., Wang, Y., Li, L. Z., Lv, Z. S., Yao, M., Lai, B. J. Ind. Microbiol. Biotechnol. 2008, 35, 1047.
(b) Machado, N. V., Omori, á. T. Biocatal. Biotransform. 2021, 39, 475.
(c) Machi, Y., Yoshida, J., Kojima, H. Results Chem. 2024, 8, 101564.
[13] Pavoković, .D., Košpić, K., Panić, M., Redovniković, I. R., Bubalo, M. C., Process Biochem., 2020, 93, 69.
[14] (a) Yadav, J. S., Nanda, S., Reddy, P. T., Rao, A. B. J. Org. Chem. 2002, 67, 3900.
(b) Yadav, J. S., Reddy, G. S. K., Sabitha, G., Krishna, A. D., Prasad, A. R., Rahaman, H. U. R., Rao, K. V., Rao, A. B. Tetrahedron: Asymmetry, 2007, 18, 717.
(c) Kazici, H. C., Bayraktar, E., Mehmetoglu, ü. Green Process Synth., 2016, 5, 131.
(d) Bai, W. J., Estrada, M. A., Gartman, J. A., Judd, A. S. ACS Med. Chem. Lett., 2023, 14, 846.
[15] (a) Liu, X., Zhang, B. L., Xia, Y. M., Xu, J. H, Acta Chim. Sin. 2009, 67, 1492 (in Chinese).
(刘湘，张宝立，夏咏梅，许建和，化学学报，2009, 67, 1492.)
(b) Maczka, W., Sołtysik, D., Wińska, K., Grabarczyk, M., Szumny A. Appl. Sci. 2018, 8, 2605.
[16] (a) Suárez-Franco, G., Hernández-Quiroz, T., Navarro-Ocaña, A., Oliart-Ros, R. M., Valerio-Alfaro, G. Biotechnol. Bioprocess Eng. 2010, 15, 441.
(b) Mohammadi, M., Yousefi, M., Habibi, Z. Biocatal. Biotransform., 2011, 29, 328.
[17] Aimar, M. L., Bordón, D. L., Formica, S. M., Cantero, J. J., Vazquez, A. M., Velasco, M. I., Rossi, L. I. Biocatal. Biotransform. 2014, 32, 348.
[18] Maczka, W. K., Mironowicz, A. Tetrahedron: Asymmetry, 2002, 13, 2299.
[19] Devendran, S., Yadav, G. D. J. Indian Chem. Soc. 2024, 101, 101111.
[20] Khan, A. U., Shahzad, M., Mushtaq, A. Naseer, M. M. RSC Adv., 2025, 15, 11863.
[21] Wu, Y. H., Wu, J. J., Wu, F. H., Prog. Biochem. Biophys. 2023, 50, 1614 (in Chinese).
(乌雅罕，吴晶晶，吴范宏，生物化学与生物物理进展，2023, 50, 1614.)
[22] (a) Xu, P. W., Wang, X., Wang, T., Cao, Z. Y., Yu, J. S., Zhou, J. Chem. Soc. Rev. 2025, 54, 9921.
(b) Ye, Z. T.; Wu, Z. W.; Zhang, X. X.; Zhou, J.; Yu, J. S. Chem. Soc. Rev. 2024, 53, 8546.
(c) Li, B. J., Ruan, Y. L., Zhu, L. Zhou, J., Yu, J. S. Chem. Commun. 2024, 60, 12302.
(d) Gong, Y., Yu, J. S., Hao, Y. J., Zhou, Y., Zhou, J. Asian J. Org. Chem. 2019, 8, 610.
(e) Hu, X. S., Yu, J. S., Zhou, J. Chem. Commun. 2019, 55, 13638.
(f) Mu, B. S., Gao, Y., Yang, F. M., Wu, W. B., Zhang, Y., Wang, X., Yu, J. S., Zhou, J. Angew. Chem. Int. Ed. 2022, 61, e202208861.
(g) Liao, L., Zhang, Y., Wu, Z. W., Ye, Z. T., Zhang, X. X., Chen, G. Y., Yu, J. S. Chem. Sci. 2022, 13, 12519.
(h) Lei, C. W., Wang, X. Y., Mu, B. S., Yu, J. S., Zhou, Y., Zhou, J. Org. Lett. 2022, 24, 8364.
(i) Zhang, X. X., Gao, Y., Zhang, Y. X., Zhou, J., Yu, J. S. Angew. Chem. Int. Ed. 2023, 62, e202217724.
(j) Zhang, Y., Yang, J. M., Ruan, Y. L., Liao, L., Ma, C., Xue, X. S., Yu, J. S. Chem. Sci. 2023, 14, 12676.
(k) Tu, Z., Peng, P. Y., Mu, B. S., Hu, X. S., Yu, J. S., Zhou, F., Zhou, J. Chin. J. Chem. 2026, 44, 1391.
(l) Zhang, X. X., Tang, D. L., Xie, X. Z., Gao, Y., Ma, C., Zhou, F., Zhou, J. Yu, J. S. Sci. China Chem. 2026, 69, 266.
(m) Ye, Z. T., Wu, Z. W., Wang, X. Y., Xiao, Q., Ma, C., Wang, X., Zhou, J., Yu, J. S. Angew. Chem. Int. Ed. 2026, e7019464.
[23] Orden, A. A., Bisogno, F. R., Giordano, O. S., Sanz, M. K. J. Mol. Catal. B: Enzym. 2008, 51, 49.
[24] 根据评委建议，为更好地衡量催化剂的效率，我们在SI第2部分提供了不同植物组织催化反应的比产率.
[25] Bruni, R., Fantin, G., Maietti, S., Medici, A., Pedrini, P., Sacchetti, G. Tetrahedron: Asymmetry, 2006, 17, 2287.
[26] El-Sayed, S.T., Salem, A.M., Shehata, A.N., Jwanny, E.W. Pakistan J. Biol. Sci. 2000, 3, 250.
[27] Lee, S. L., Shih, H. T., Chi, Y. C., Li, Y. P., Yin, S. J. Chem. Biol. Interact. 2011, 191, 26.
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