Enantio- and Diastereoselective Synthesis of Chiral Syn-Aryl beta-Hydroxy alpha-Amino Esters via Biocatalytic Dynamic Reductive Kinetic Resolution

Development of an efficient, stereoselective, sustainable synthesis of chiral aryl beta-hydroxy alpha-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 ke...

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Bibliographic Details
Published inAsian journal of organic chemistry Vol. 10; no. 7; pp. 1700 - 1703
Main Authors Zhang, Qing-Chun, Lu, Zuo-Lin, Hu, Chen, Zhu, Kejie, Jiang, Meifen, Huang, Zedu, Chen, Fener
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 01.07.2021
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
CORE
amino ester
ASYMMETRIC-SYNTHESIS
HYDROGENATION
chiral syn-aryl &#946
hydroxy &#945
ENANTIOSELECTIVE SYNTHESIS
dynamic reductive kinetic resolution
thiamphenicol
ketoreductase
CATALYST
stereoselective
ELIGLUSTAT
EFFICIENT
DERIVATIVES
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Summary:Development of an efficient, stereoselective, sustainable synthesis of chiral aryl beta-hydroxy alpha-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 alpha-amino beta-keto esters 6, furnishing 20 structurally diverse chiral syn-aryl beta-hydroxy alpha-amino esters (syn-(2S,3R)-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).
ISSN:2193-5807
2193-5815
DOI:10.1002/ajoc.202100276