Prostaglandin photoaffinity probes: Synthesis and binding affinity of C-18 substituted PGF(2α) prostanoids bearing a perfluorinated aryl azide

C-18 Phenoxy analogs of prostaglandin F(2α) (PGF(2α)) that possessed a perfluorinated aryl azide and an aryl iodide sustituent were synthesized and evaluated as potential photoaffinity probes for PGF(2α). Prior studies indicated that only hydrophobic modifications in the ω-side chain of PGF(2α) were compatible with high binding affinity, and this finding excluded the use of a hydroxyl-substituted C-18 phenoxy group as an activated aryl ring capable of radioiodination. Consequently, an alternate means of introducing the iodine substituent using an ipso-substitution of a trimethylsilyl arene was developed. Although this strategy was successful from a synthetic perspective, the potential PGF(2α) photoaffinity probe, (15S)-18-[3'-((4''-azide-2'',3'',5'',6''- tetrafluorophenyl)methoxy)methyl-5'-iodophenoxy]-19,20-bisnorprostaglandin F(2α), exhibited only marginal competitive binding with [³H]-PGF(2α) to ovine luteal cells and to plasma membranes of bovine corpora lutea. The hydrophobic but bulky C-18 substituent was presumably incompatible with effective receptor binding.