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