Synthesis of cyclic phosphonate analogues of (lyso)phosphatidic acid using a ring-closing metathesis reaction

J Org Chem. 2006 Aug 4;71(16):6061-6. doi: 10.1021/jo0607919.

Abstract

We describe a versatile and efficient method for the preparation of acyloxy-substituted six-membered cyclic phosphonates using the ring-closing metathesis. After closure, the key cyclic phosphonate intermediate was dihydroxylated and converted to a new class of conformationally constrained PA and LPA analogues. The oleoyloxy-substituted cyclic phosphonate 4 had unique receptor-selective properties as a ligand, showing partial activation of the LPA2 GPCR and weak antagonism of the LPA1 GPCR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cyclization
  • Lysophospholipids / chemistry*
  • Lysophospholipids / metabolism
  • Molecular Structure
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry*
  • Receptors, Lysophosphatidic Acid / metabolism

Substances

  • Lysophospholipids
  • Organophosphonates
  • Receptors, Lysophosphatidic Acid