Plastoquinone is a key electron carrier in photosynthesis and an essential cofactor for the biosynthesis of carotenoids. p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a vital enzymatic step in plastoquinone biosynthesis that is the target of triketone herbicides, such as those derived from the pharmacophore backbone of the natural product leptospermone. In this work, the inhibitory activity of a series of 2-acyl-cyclohexane-1,3-diones congeners derived from Peperomia natural products was tested on plant HPPD. The most active compound was a 2-acyl-cyclohexane-1,3-dione with a C₁₁ alkyl side chain (5d; I₅₀app: 0.18 ± 0.02 μM) that was slightly more potent than the commercial triketone herbicide sulcotrione (I₅₀app: 0.25 ± 0.02 μM). QSAR analysis and docking studies were performed to further characterize the key structural features imparting activity. A 1,3-dione feature was required for inhibition of HPPD. Molecules with a side chain of 11 carbons were found to be optimal for inhibition, while the presence of a double bond, hydroxy, or methyl beyond the required structural features on the cyclohexane ring generally decreased HPPD inhibiting activity.

中文翻译：

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Peperomia天然产物2-酰基环己烷1,3-二酮同系物对植物对羟基苯丙酮酸双加氧酶除草分子靶位点的合成及活性

质体醌是光合作用的关键电子载体，也是类胡萝卜素生物合成的重要辅助因子。对羟基苯丙酮酸双加氧酶 (HPPD) 是质体醌生物合成中的重要酶促步骤，它是三酮类除草剂的目标，例如源自天然产物细精子素的药效团骨架的除草剂。在这项工作中，一系列来自胡椒天然产物的 2-酰基-环己烷-1,3-二酮同系物对植物 HPPD 的抑制活性进行了测试。最活跃的化合物是具有 C ₁₁烷基侧链的 2-酰基-环己烷-1,3-二酮 ( 5d ; I ₅₀ app: 0.18 ± 0.02 μM)，比商业三酮类除草剂磺草酮 (I ₅₀应用：0.25 ± 0.02 μM）。进行了 QSAR 分析和对接研究，以进一步表征赋予活性的关键结构特征。抑制 HPPD 需要 1,3-二酮特征。发现具有 11 个碳侧链的分子最适合抑制，而在环己烷环上超出所需结构特征的双键、羟基或甲基的存在通常会降低 HPPD 抑制活性。