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Enantio‐ and Diastereoselective Synthesis of Chiral Syn ‐Aryl β‐Hydroxy α‐Amino Esters via Biocatalytic Dynamic Reductive Kinetic Resolution
Author(s) -
Zhang QingChun,
Lu ZuoLin,
Hu Chen,
Zhu Kejie,
Jiang Meifen,
Huang Zedu,
Chen Fener
Publication year - 2021
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.202100276
Subject(s) - kinetic resolution , chemistry , aryl , enantioselective synthesis , stereoselectivity , yield (engineering) , amino acid , chirality (physics) , combinatorial chemistry , stereochemistry , organic chemistry , catalysis , biochemistry , alkyl , materials science , chiral symmetry breaking , physics , quantum mechanics , quark , nambu–jona lasinio model , metallurgy
Abstract Development of an efficient, stereoselective, sustainable synthesis of chiral aryl β‐hydroxy α‐amino acids and their derivatives is of paramount importance, owing to the broad utility of these molecules in pharmaceutical application and asymmetric synthesis. We report a systematic study on ketoreductase (KRED)‐catalyzed dynamic reductive kinetic resolution (DYRKR) of aryl α‐amino β‐keto esters 6 , furnishing 20 structurally diverse chiral syn ‐aryl β‐hydroxy α‐amino esters ( syn ‐(2 S ,3 R )‐ 7 ) in moderate‐to‐excellent isolated yield (up to 93%), along with moderate‐to‐excellent diastereoselectivity (up to >99 : 1 dr) and excellent enantioselectivity (mostly >99% ee). The practical synthesis potential of our developed method was showcased by the asymmetric, chemo‐enzymatic total synthesis of thiamphenicol ( 1 ).