Instituto de Tecnología Química, Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, 46022, Valencia, Spain.
Chemistry. 2021 Jul 21;27(41):10766-10775. doi: 10.1002/chem.202100967. Epub 2021 Jun 8.
Zr-containing MOF-808 is a very promising heterogeneous catalyst for the selective reduction of ketosteroids to the corresponding hydroxysteroids through a Meerwein-Ponndorf-Verley (MPV) reaction. Interestingly, the process leads to the diastereoselective synthesis of elusive 17α-hydroxy derivatives in one step, whereas most chemical and biological transformations produce the 17β-OH compounds, or they require several additional steps to convert 17β-OH into 17α-OH by inverting the configuration of the 17 center. Moreover, MOF-808 is found to be stable and reusable; it is also chemoselective (only keto groups are reduced, even in the presence of other reducible groups such as C=C bonds) and regioselective (in 3,17-diketosteroids only the keto group in position 17 is reduced, while the 3-keto group remains almost intact). The kinetic rate constant and thermodynamic parameters of estrone reduction to estradiol have been obtained by a detailed temperature-dependent kinetic analysis. The results evidence a major contribution of the entropic term, thus suggesting that the diastereoselectivity of the process is controlled by the confinement of the reaction inside the MOF cavities, where the Zr active sites are located.
Zr 金属有机骨架化合物（MOF-808）是一种很有前途的非均相催化剂，可通过 Meerwein-Ponndorf-Verley（MPV）反应将酮甾体选择性还原为相应的羟基甾体。有趣的是，该过程可以一步合成难以获得的 17α-羟基衍生物，而大多数化学和生物转化只会产生 17β-OH 化合物，或者需要通过多个额外步骤将 17β-OH 转化为 17α-OH，从而翻转 17 位中心的构型。此外，MOF-808 被发现是稳定且可重复使用的；它还具有化学选择性（仅还原酮基，即使存在其他可还原基团，如 C=C 键）和区域选择性（在 3,17-二酮甾体中，仅 17 位的酮基被还原，而 3-酮基几乎保持完整）。通过详细的温度依赖动力学分析，获得了雌酮还原为雌二醇的动力学速率常数和热力学参数。结果表明，熵项的贡献很大，这表明该过程的非对映选择性受反应在 MOF 腔内部的限制控制，Zr 活性位点位于 MOF 腔内部。
