Prostaglandin Photoaffinity Probes: Synthesis and Biological Activity of Azide-Substituted 16-Phenoxy- and 17-Phenyl-PGF2α Prostaglandins

Article abstract of DOI:10.1021/jm00121a046

The development of a prostaglandin PGF_2α photoaffinity probe led to the synthesis and biological evaluation of azide-substituted 17-phenyl-18,19,20-trinorprostaglandin F_2α and 16-phenoxy-17,18,19,20-tetranorprostaglandin F_2α derivatives.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_2α, 16-(5-azido-3-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F_2α, and 16-(4-azido-2-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F_2α were 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_2α derivative delivered 17-(4-azido-3-iodophenyl)-18,19,20-trinorprostaglandin F_2α, which exhibited competitive binding with natural <3H>PGF_2α to ovine luteal cells and to plasma membranes of bovine corpora lutea. <125I>-17-(4-Azido-3-iodophenyl)-18,19,20-trinorprostaglandin F_2α was utilized in a preliminary photoaffinity cross-linking experiment.