Synthesis of p-hydroxyubenimex

J Antibiot (Tokyo). 1987 Aug;40(8):1165-9. doi: 10.7164/antibiotics.40.1165.

Abstract

p-Hydroxyubenimex, (2S,3R)-3-amino-2-hydroxy-4-p-hydroxyphenylbutyryl-L-leucine, was synthesized starting from D-tyrosine. The structure and stereochemistry of the synthesized product were confirmed by comparison with p-hydroxyubenimex that was chemically transformed from ubenimex, an aminopeptidase inhibitor of microbial origin. Compared to ubenimex, p-hydroxyubenimex is more active against aminopeptidase B but less active against leucine aminopeptidase. By using the synthetic p-hydroxyubenimex as a reference sample, one of the metabolites of ubenimex was identified as p-hydroxyubenimex. The (2R,3R)-stereoisomer of p-hydroxyubenimex was also prepared. However, its activity against aminopeptidases was much weaker.

MeSH terms

  • Aminopeptidases / antagonists & inhibitors
  • Anti-Bacterial Agents / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Hydroxylation
  • Leucine / analogs & derivatives*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tyrosine

Substances

  • Anti-Bacterial Agents
  • Tyrosine
  • Aminopeptidases
  • Leucine
  • ubenimex