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

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)-2awas 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, Daucus carota subsp. Sativus, Coriandrum sativum, asymmetric reduction