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

研究论文

三红胡萝卜和香菜介导的氟代芳香酮不对称还原反应

  • 唐允浩 ,
  • 周齐治 ,
  • 王韬 ,
  • 邱智恒 ,
  • 乐效靖 ,
  • 张燕 ,
  • 余金生
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  • a华东师范大学化学与分子工程学院 上海分子治疗与新药创制工程技术研究中心,绿色化学与化工过程绿色化上海市重点实验室 上海 200062;
    b华东师范大学第二附属中学附属初级中学 上海 200241

收稿日期: 2026-05-26

  网络出版日期: 2026-07-10

基金资助

上海市农业科技创新项目(No. HNK(T2023302))和国家自然科学基金(No. 22471073)

收起

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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摘要

氟代手性仲醇是许多医药、农药及生物活性分子的关键结构单元,其绿色、高效、高选择性的制备对药物合成工艺创新具有重要意义。近年来,植物全细胞生物催化已成为通过不对称还原酮类化合物合成光学活性手性仲醇的一种新策略,具有催化剂廉价易得、反应条件温和、环境友好等优点。然而,利用该方法制备氟代手性仲醇的研究仍较为有限。本文系统考察了多种廉价易得的蔬菜植物组织对氟代芳香酮的不对称还原性能,发现三红胡萝卜能高效、高选择性地还原多种氟代酮,以中等到良好的分离产率（21%~85%）及中等到优秀的对映选择性（59~>99% ee）获得相应氟代手性仲醇,其中包含多个可用于合成医药和农药分子的关键中间体。该方法具有良好的放大合成潜力,如1克间三氟甲基苯乙酮1a经三红胡萝卜催化还原后,能以76%分离收率和大于99% ee获得0.766克目标产物(S)-2a。尤为值得一提的是,本研究首次发现香菜根可作为全细胞生物催化剂,实现氟代酮的高选择性还原,且在部分底物中表现出优于胡萝卜的催化效果,为植物全细胞催化不对称合成提供了全新的催化剂资源。

关键词： 氟代手性仲醇; 植物全细胞催化; 三红胡萝卜; 香菜; 不对称还原反应

本文引用格式

唐允浩 , 周齐治 , 王韬 , 邱智恒 , 乐效靖 , 张燕 , 余金生 . 三红胡萝卜和香菜介导的氟代芳香酮不对称还原反应[J]. 化学学报, 0 : 3 -3 . DOI: 10.6023/A26050176

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

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