Catalytic Syn-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol.
Catalytic Syn-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol.
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DOI：
10.1021/acs.joc.1c01124
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Yingqi Xia;Meifen Jiang;Min-jie Liu;Yan Zhang;Hong-Yu Qu;Tong Xiong;Huashan Huang;Dang Cheng;Fen‐er Chen
中科院分区：
文献类型：
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作者：
Yingqi Xia;Meifen Jiang;Min-jie Liu;Yan Zhang;Hong-Yu Qu;Tong Xiong;Huashan Huang;Dang Cheng;Fen‐er Chen
报道了一种基于关键的催化顺式选择性亨利反应的高效和高非对映选择性合成（-）-氯霉素、（-）-叠氮霉素、（+）-甲砜霉素和（+）-氟苯尼考的统一策略。首次探索了配体使能的铜（II）催化的硝基乙醇的芳基醛亨利反应的立体化学，以锻造具有优异立体控制的具有邻位立构中心的具有挑战性的顺式-2-氨基-1，3-二醇结构单元。多步连续流动操作进行，以实现有效的不对称合成这个家庭的氯霉素抗生素。
A unified strategy for an efficient and high diastereo- and enantioselective synthesis of (-)-chloramphenicol, (-)-azidamphenicol, (+)-thiamphenicol, and (+)-florfenicol based on a key catalytic syn-selective Henry reaction is reported. The stereochemistry of the ligand-enabled copper(II)-catalyzed aryl aldehyde Henry reaction of nitroethanol was first explored to forge a challenging syn-2-amino-1,3-diol structure unit with vicinal stereocenters with excellent stereocontrol. Multistep continuous flow manipulations were carried out to achieve the efficient asymmetric synthesis of this family of amphenicol antibiotics.