Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: application of catalytic asymmetric phase-transfer reaction

Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5433-8. doi: 10.1073/pnas.0307154101. Epub 2004 Mar 2.

Abstract

Aeruginosin 298-A was isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-298) and is an equipotent thrombin and trypsin inhibitor. A variety of analogs were synthesized to gain insight into the structure-activity relations. We developed a versatile synthetic process for aeruginosin 298-A as well as several attractive analogs, in which all stereocenters were controlled by catalytic asymmetric phase-transfer reaction promoted by two-center asymmetric catalysts and catalytic asymmetric epoxidation promoted by a lanthanide-BINOL complex. Furthermore, serine protease inhibitory activities of aeruginosin 298-A and its analogs were examined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Catalysis
  • Epoxy Compounds / chemistry
  • Inhibitory Concentration 50
  • Leucine / analogs & derivatives*
  • Leucine / chemical synthesis*
  • Leucine / chemistry
  • Leucine / pharmacology*
  • Naphthols / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Trypsin Inhibitors / chemical synthesis*
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / pharmacology*

Substances

  • BINOL, naphthol
  • Epoxy Compounds
  • Naphthols
  • Trypsin Inhibitors
  • aeruginosin 298-A
  • Leucine