title: Synthesis of cyclic phosphonate analogues of (lyso)phosphatidic acid using a ring-closing metathesis reaction.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257, USA.
authors.forename: Honglu
authors.initials: H
authors.lastname: Zhang
authors.forename: Ryoko
authors.initials: R
authors.lastname: Tsukuhara
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
mesh_terms: D003500:Cyclization; D008246:Lysophospholipids / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D063065:Organophosphonates; D049368:Receptors, Lysophosphatidic Acid