Catalytic <i>Syn</i>-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (−)-Chloramphenicol, (−)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol
Ying‐Qi Xia, Meifen Jiang, Minjie Liu, Yan Zhang, Hongmin Qu, Tong Xiong, Hua‐Shan Huang, Dang Cheng, Fen‐Er Chen
Abstract
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.
Topics & Concepts
ThiamphenicolFlorfenicolChloramphenicolAntibioticsMicrobiologyVirologyBiologyInnovative Microfluidic and Catalytic Techniques InnovationSynthesis and Catalytic ReactionsChemical Synthesis and Analysis