Department of Chemistry, College of Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States.
Steroids. 2011 Feb;76(3):291-300. doi: 10.1016/j.steroids.2010.11.010. Epub 2010 Dec 8.
A variety of unnatural bile acid derivatives (9a-9f) was synthesized and used to examine the specificity with which the sea lamprey (Petromyzon marinus) olfactory system detects these compounds. These compounds are analogs of petromyzonol sulfate (PS, 1), a component of the sea lamprey migratory pheromone. Both the stereochemical configuration at C5 (i.e., 5α vs. 5β) and the extent and sites of oxygenation (hydroxylation or ketonization) of the bile acid derived steroid skeleton were evaluated by screening the compounds for olfactory activity using electro-olfactogram recording. 5β-Petromyzonol sulfate (9a) elicited a considerable olfactory response at sub-nanomolar concentration. In addition, less oxygenated systems (i.e., 9b-9e) elicited olfactory responses, albeit with less potency. The sea lamprey sex pheromone mimic 9f (5β-3-ketopetromyzonol sulfate) was also examined and found to produce a much lower olfactory response. Mixture studies conducted with 9a and PS (1) suggest that stimulation is occurring via similar modes of activation, demonstrating a relative lack of specificity for recognition of the allo-configuration (i.e., 5α) in sea lamprey olfaction. This attribute could facilitate design of pheromone analogs to control this invasive species.
合成了多种非天然胆酸衍生物（9a-9f），并将其用于检测海七鳃鳗（Petromyzon marinus）嗅觉系统对这些化合物的特异性。这些化合物是海七鳃鳗洄游信息素组成部分之一—— petromyzonol 硫酸盐（PS，1）的类似物。通过使用电嗅觉图记录筛选化合物的嗅觉活性，评估了胆酸衍生甾体骨架在 C5 处的立体化学构型（即 5α 与 5β）以及氧（羟基化或酮化）化程度和位置。5β-Petromyzonol 硫酸盐（9a）在亚纳摩尔浓度下就引发了相当大的嗅觉反应。此外，含氧程度较低的系统（即 9b-9e）也引发了嗅觉反应，尽管效力较低。还对海七鳃鳗性信息素类似物 9f（5β-3-酮 petromyzonol 硫酸盐）进行了研究，发现其产生的嗅觉反应要低得多。用 9a 和 PS（1）进行的混合物研究表明，刺激是通过类似的激活模式发生的，这表明在海七鳃鳗嗅觉中对 allo-构型（即 5α）的识别缺乏特异性。这种特性可以促进设计信息素类似物来控制这种入侵物种。
