Fruhmann Philipp, Weigl-Pollack Theresa, Mikula Hannes, Wiesenberger Gerlinde, Adam Gerhard, Varga Elisabeth, Berthiller Franz, Krska Rudolf, Hametner Christian, Fröhlich Johannes
Institute of Applied Synthetic Chemistry, Vienna University of Technology (VUT), Getreidemarkt 9/163, 1060 Vienna, Austria.
Org Biomol Chem. 2014 Jul 28;12(28):5144-50. doi: 10.1039/c4ob00458b.
Methylthiodeoxynivalenol (MTD), a novel derivative of the trichothecene mycotoxin deoxynivalenol (DON), was prepared by applying a reliable procedure for the formal Michael addition of methanethiol to the conjugated double bond of DON. Structure elucidation revealed the preferred formation of the hemiketal form of MTD by intramolecular cyclisation between C8 and C15. Computational investigations showed a negative total reaction energy for the hemiketalisation step and its decrease in comparison with theoretical model compounds. Therefore, this structural behaviour seems to be a general characteristic of thia-Michael adducts of type B trichothecenes. MTD was shown to be less inhibitory for a reticulocyte lysate based in vitro translation system than the parent compound DON, which supports the hypothesis that trichothecenes are detoxified through thia-adduct formation during xenobiotic metabolism.
甲基硫代脱氧雪腐镰刀菌烯醇（MTD）是单端孢霉烯族真菌毒素脱氧雪腐镰刀菌烯醇（DON）的一种新型衍生物，它是通过一种可靠的方法，将甲硫醇正式迈克尔加成到DON的共轭双键上制备而成。结构解析表明，MTD通过C8和C15之间的分子内环化优先形成半缩酮形式。计算研究表明，半缩酮化步骤的总反应能量为负，与理论模型化合物相比有所降低。因此，这种结构行为似乎是B型单端孢霉烯硫杂-迈克尔加成物的一个普遍特征。结果表明，MTD对基于网织红细胞裂解物的体外翻译系统的抑制作用比母体化合物DON小，这支持了在异源生物代谢过程中，单端孢霉烯族毒素通过硫杂加成物的形成而解毒的假说。
