School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Waihuang East Road No. 232, Guangzhou 510006, China.
School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Waihuang East Road No. 232, Guangzhou 510006, China.
Molecules. 2022 Jul 28;27(15):4842. doi: 10.3390/molecules27154842.
Phytophenol dimerization, which is a radical-mediated coupling reaction, plays a critical role in many fields, including lignin biosynthesis. To understand the reaction, 2,2-diphenyl-1-picrylhydrazyl radical was used to initiate a series of phytophenol dimerization reactions in methanol. The products were identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) analysis in situ. The identified products mainly included biphenols, magnolol, honokiol, gingerol 6,6'-dimers, 3,6-dimethoxylcatechol β,β' dimer, euphorbetin, bis-eugenol, dehydrodiisoeugenol, -viniferin, (+) pinoresinol, and (-) pinoresinol. Structure-function relationship analysis allowed four basic rules to be defined: -excluded, C-C bonding domination, -diOH co-activation, and exocyclic C=C involvement. The exocyclic C=C involvement, however, required conjugation with the phenolic core and the -site of the -OH group, to yield a furan-fused dimer with two chiral centers. Computational chemistry indicated that the entire process was completed via a radical coupling reaction and an intramolecular conjugate addition reaction. Similar results were also found for the horseradish peroxidase (HRP)-catalyzed coniferyl alcohol dimerization, which produced (+) and (-) pinoresinols (but no (-) epipinoresinol), suggesting that the HRP-catalyzed process was essentially an exocyclic C=C-involved phytophenol dimerization reaction. The reaction was highly diastereoselective. This was attributed to the intramolecular reaction, which prohibited -attack. The four basic rules and diastereoselectivity can explain and even predict the main products in various chemical and biological events, especially oxidase-catalyzed lignin cyclization.
植物酚二聚化是一种自由基介导的偶联反应，在许多领域都起着至关重要的作用，包括木质素生物合成。为了研究该反应，我们在甲醇中使用 2,2-二苯基-1-苦基肼自由基引发了一系列植物酚二聚化反应。通过超高效液相色谱-电喷雾电离四极杆飞行时间串联质谱（UHPLC-ESI-Q-TOF-MS/MS）分析原位鉴定了产物。鉴定的产物主要包括联苯酚、厚朴酚、和厚朴酚、姜辣素 6,6′-二聚体、3,6-二甲氧基儿茶酚 β,β′二聚体、 euphorbetin、双丁香酚、脱氢二异丁香酚、-viniferin、（+）松脂醇和（-）松脂醇。结构-功能关系分析确定了四条基本规则：排除规则、C-C 键主导规则、-OH 协同激活规则和环外 C=C 参与规则。然而，环外 C=C 参与需要与酚核和 -OH 基团的 - 位共轭，生成具有两个手性中心的呋喃稠合二聚体。计算化学表明，整个过程是通过自由基偶联反应和分子内共轭加成反应完成的。辣根过氧化物酶（HRP）催化的松柏醇二聚化也得到了类似的结果，生成了（+）和（-）松脂醇（但没有（-）表松脂醇），这表明 HRP 催化的过程本质上是一个环外 C=C 参与的植物酚二聚化反应。该反应具有高度的非对映选择性。这归因于禁止 - 进攻的分子内反应。这四条基本规则和非对映选择性可以解释甚至预测各种化学和生物事件中的主要产物，特别是氧化酶催化的木质素环化。
