Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (−)-Chloramphenicol, (−)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride
Jinxin Liu, Yaling Li, Miaolin Ke, Minjie Liu, Pingping Zhan, You‐Cai Xiao, Fen‐Er Chen
Abstract
The asymmetric synthesis of (−)-chloramphenicol, (−)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired trans-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of syn-vicinal amino alcohols in the amphenicol family.
Topics & Concepts
ChemistryEnantioselective synthesisThiamphenicolVicinalStereochemistryChloramphenicolStereocenterAldol reactionCinchonaCombinatorial chemistryAntibioticsOrganic chemistryCatalysisBiochemistryChemical Synthesis and AnalysisInnovative Microfluidic and Catalytic Techniques InnovationSynthesis and Catalytic Reactions