A practical synthesis and biological evaluation of 9-halogenated PGF analogues

Bioorg Med Chem. 2002 Jun;10(6):1883-94. doi: 10.1016/s0968-0896(02)00008-1.

Abstract

A series of 9-halo PGF analogues 1-2 and 5-13 were synthesized and biologically evaluated. Among the compounds, 2 was the best EP2-receptor agonist. A practical method of synthesizing 2 via the Julia olefination of an aldehyde 3 with an optically active sulfone 4, which was prepared by Sharpless asymmetric epoxidation of 15, was developed. Other 9-halogenated PGF analogues were synthesized essentially by the same procedure and evaluated. The absolute configuration of 16-OH of 2 was determined as S by the X-ray analysis of a salt consisting of a 1/1 molar ratio of 2 and L-lysine.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Crystallography, X-Ray
  • Cyclic AMP / metabolism
  • Halogens / chemistry*
  • Molecular Conformation
  • Molecular Structure
  • Prostaglandins F, Synthetic / chemical synthesis*
  • Prostaglandins F, Synthetic / chemistry
  • Prostaglandins F, Synthetic / pharmacology*
  • Receptors, Prostaglandin E / metabolism
  • Second Messenger Systems / drug effects
  • Structure-Activity Relationship

Substances

  • Halogens
  • Prostaglandins F, Synthetic
  • Receptors, Prostaglandin E
  • Cyclic AMP