Prostaglandin photoaffinity probes: synthesis and biological activity of azide-substituted 16-phenoxy- and 17-phenyl-PGF2.alpha. prostaglandins

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Abstract
The development of a prostaglandin PGF2.alpha. photoaffinity probe led to the synthesis and biological evaluation of azide-substituted 17-phenyl-18,19,20-trinorprostaglandin F2.alpha. and 16-phenoxy-17,18,19,20-tetranorprostaglandin F2.alpha. 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 F2.alpha., 16-(5-azido-3-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2.alpha., and 16-(4-azido-2-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2.alpha. 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 F2.alpha. derivative delivered 17-(4-azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2.alpha., which exhibited competitive binding with natural [3H]PGF2.alpha. to ovine luteal cells and to plasma membranes of bovine corpora lutea. [125I]-17-(4-Azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2.alpha. was utilized in a preliminary photoaffinity cross-linking experiment.