Enzymatic synthesis of L-6-hydroxynorleucine

Bioorg Med Chem. 1999 Oct;7(10):2247-52. doi: 10.1016/s0968-0896(99)00158-3.

Abstract

L-6-Hydroxynorleucine, a key chiral intermediate used for synthesis of a vasopeptidase inhibitor, was prepared in 89% yield and > 99% optical purity by reductive amination of 2-keto-6-hydroxyhexanoic acid using glutamate dehydrogenase from beef liver. In an alternate process, racemic 6-hydroxynorleucine produced by hydrolysis of 5-(4-hydroxybutyl)hydantoin was treated with D-amino acid oxidase to prepare a mixture containing 2-keto-6-hydroxyhexanoic acid and L-6-hydroxynorleucine followed by the reductive amination procedure to convert the mixture entirely to L-6-hydroxynorleucine, with yields of 91 to 97% and optical purities of > 99%.

MeSH terms

  • Animals
  • Catalase / chemistry
  • Catalase / metabolism
  • Cattle
  • D-Amino-Acid Oxidase / chemistry
  • D-Amino-Acid Oxidase / metabolism
  • Glucose 1-Dehydrogenase
  • Glucose Dehydrogenases / chemistry
  • Glucose Dehydrogenases / metabolism
  • Glutamate Dehydrogenase / chemistry
  • Glutamate Dehydrogenase / metabolism
  • Kidney / enzymology
  • Liver / enzymology
  • Mitosporic Fungi / enzymology
  • NAD / metabolism
  • Norleucine / analogs & derivatives*
  • Norleucine / chemical synthesis

Substances

  • NAD
  • epsilon-hydroxynorleucine
  • Norleucine
  • Glucose Dehydrogenases
  • Glucose 1-Dehydrogenase
  • Catalase
  • Glutamate Dehydrogenase
  • D-Amino-Acid Oxidase