Prostaglandin Photoaffinity Probes: Synthesis And Biological Activity of Azide-Substituted 16-Phenoxy- and 17-Phenyl-PGF_2αProstaglandins

The development of a prostaglandin PGF_2aphotoaffinity probe led to the synthesis and biological evaluation of azide-substituted 17-phenyl-18,19,20-trinorprostaglandin F_2aand 16-phenoxy-17,18,19,20-tetranorprostaglandin E_2aderivatives. Two approaches for the preparation of iodinated versions of these prostaglandins were evaluated: (1) iodination of a phenyl azide bearing an activating hydroxyl group and (2) iodination of an aniline precursor to the phenyl azide group and subsequent conversion of the aniline to the phenyl azide. In the first approach, 17-(4-azido-2-hydroxyphenyl)-18,19,20-trinorprostaglandin F_2a, 16-(5-azido-3-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F_2a, and 16-(4-azido-2-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F_2awere prepared by using the Corey synthesis, but were biologically inactive presumably as a result of the hydrophilic phenolic hydroxyl group. In the second approach, the iodination of a 17-(4-aminophenyl)-18,19,20-trinorprostaglandin F_2aderivative delivered 17-(4-azido-3-iodophenyl)-18,19,20-trinorprostaglandin F₂α, which exhibited competitive binding with natural [³H]PGF₂α to ovine luteal cells and to plasma membranes of bovine corpora lutea. [¹²⁵I]-17-(4-Azido-3-iodophenyl)-18,19,20-trinorprostaglandin F_2awas utilized in a preliminary photoaffinity cross-linking experiment.