A practical synthesis of 5-lipoxygenase inhibitor MK-0633

J Org Chem. 2010 Jun 18;75(12):4154-60. doi: 10.1021/jo100561u.

Abstract

Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).

MeSH terms

  • Arachidonate 5-Lipoxygenase / chemistry
  • Benzenesulfonates / chemical synthesis*
  • Benzenesulfonates / chemistry
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Lipoxygenase Inhibitors* / chemical synthesis*
  • Lipoxygenase Inhibitors* / chemistry
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Stereoisomerism

Substances

  • Benzenesulfonates
  • Benzopyrans
  • Lipoxygenase Inhibitors
  • MK-0633 p-toluenesulfonate
  • Oxadiazoles
  • Arachidonate 5-Lipoxygenase
  • 4-toluenesulfonic acid