Pyridoxal-Catalyzed Racemization of α-Aminoketones Enables the Stereodivergent Synthesis of 1,2-Amino Alcohols Using Ketoreductases

Jingzhe Cao, Todd K. Hyster

Research output: Contribution to journalArticle

Abstract

Differentially substituted 1,2-amino alcohols are a prevalent motif in a variety of pharmaceutical and agrochemical molecules. Dynamic kinetic resolutions (DKRs) that involve the asymmetric reduction of α-amino ketones are attractive for preparing this motif; however, methods for racemizing the stereogenic α-carbon under mild conditions are underdeveloped. Here we report a chemoenzymatic DKR involving ketoreductases (KREDs), in which pyridoxal-5-phosphate (PLP) is used to catalyze racemization of the starting racemic α-aminoketone. This strategy enables access to a variety of 1,2-amino alcohols with high levels of diastereo- and enantioselectivity. Using commercially available KREDs, all four possible stereoisomers can be accessed, highlighting a benefit to this approach.

Original languageEnglish (US)
Pages (from-to)6171-6175
Number of pages5
JournalACS Catalysis
Volume10
Issue number11
DOIs
StatePublished - Jun 5 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • biocatalysis
  • dynamic kinetic resolution
  • ketoreductase
  • pyridoxal
  • racemization

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