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J Med Chem. 2000 Sep 7;43(18):3400-7.

Synthesis and biological activity of a novel 11a-homo (cyclohexyl) prostaglandin.

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Departments of Medicinal Chemistry and Molecular Pharmacology, Alcon Laboratories, Inc., 6201 South Freeway, MS R2-39, Ft. Worth, Texas 76134, USA.


The racemic cyclohexane-for-cyclopentane ring substitution analogue of the potent prostaglandin FP agonist cloprostenol (7) was synthesized from cyclohexenediol 11 in 21 steps and 0.07% yield. In a prostaglandin FP receptor-linked second-messenger assay, racemic analogue 7 exhibited an EC(50) value of 319 nM (72% response relative to cloprostenol); the corresponding values for PGF(2)(alpha) and cloprostenol were 23 nM (91% relative response) and 1 nM (defined as 100% response), respectively. Key features of the synthesis were the selective manipulation of four hydroxyl groups to direct independent elaboration of the alpha and omega chains and a new method for synthesis of aryloxy-terminated omega chains involving Horner-Emmons elongation of an aldehyde to a methyl enone, regioselective bromination adjacent to the carbonyl, and phenoxide displacement of bromide.

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