5-脱氧莰非醇 | 2034-65-3

• 物质功能分类: 化学试剂 - 有机试剂 - 三环化合物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 5-脱氧莰非醇
• 中文别名: 3,7,4-三羟基黄酮；3,7,4'-三羟基黄酮(5-Deoxykaempferol)
• 英文名称: resokaempferol
• 英文别名: 3,4',7-Trihydroxyflavon；3,7,4'-Trihydroxyflavone；3,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
• CAS: 2034-65-3
• 化学式: C₁₅H₁₀O₅
• 分子量: 270.241
• InChiKey: OBWHQJYOOCRPST-UHFFFAOYSA-N

物化性质

• 熔点：
  310-311°C
• 沸点：
  539.7±50.0 °C(Predicted)
• 密度：
  1.579±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）
• LogP：
  2.490 (est)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

Resokaempferol 已知的人类代谢物包括 (2S,3S,4S,5R)-6-[4-(3,7-二羟基-4-氧代色酮-2-基)苯氧基]-3,4,5-三羟基氧杂环己烷-2-羧酸。

Resokaempferol has known human metabolites that include (2S,3S,4S,5R)-6-[4-(3,7-dihydroxy-4-oxochromen-2-yl)phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2914501900
• 储存条件：
  存放于室温、密闭且干燥的环境中。

制备方法与用途

生物活性研究发现，3,7,4'-三羟基黄酮是从/rsshuanica var. roxburghiana中分离得到的一种具有DNA断链活性的黄酮类化合物。

反应信息

• 作为反应物：
  描述：

  5-脱氧莰非醇 在 异丙基-beta-D-硫代半乳糖吡喃糖苷 作用下， 反应 18.0h， 生成 漆黄素
  参考文献：
  名称：

  [EN] MICROBIAL PRODUCTION OF THE FLAVONOIDS GARBANZOL, RESOKAEMPFEROL AND FISETIN
  [FR] PRODUCTION MICROBIENNE DES FLAVONOÏDES GARBANZOL, RESOKAEMPFÉROL ET FISÉTINE

  摘要：

  公开号：

  WO2016071505A9
• 作为产物：
  描述：

  1-(2,4-二羟基苯基)-2-甲氧基-1-乙酮 在 氢碘酸 、 乙酸酐 、 sodium anisate 作用下， 生成 5-脱氧莰非醇
  参考文献：
  名称：

  Rao; Seshadri, Proceedings - Indian Academy of Sciences, Section A, 1948, # 28, p. 96

  摘要：

  DOI：

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons
  作者：Goran Benković、Hrvoje Rimac、Željan Maleš、Siniša Tomić、Zoran Lončar、Mirza Bojić

  DOI：10.5562/cca3528

  日期：——

  One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity

  代谢酶中最重要的一组之一是细胞色素P450超家族。这些酶在催化多样性方面很重要
• Uridine Diphosphate Glucuronosyltransferase Isoform-Dependent Regiospecificity of Glucuronidation of Flavonoids
  作者：Rashim Singh、Baojian Wu、Lan Tang、Ming Hu

  DOI：10.1021/jf1041454

  日期：2011.7.13

  objective of this study was to determine the regiospecificity of the important uridine diphosphate glucuronosyltransferase (UGT) isoforms responsible for the glucuronidation of flavones and flavonols. We systematically studied the glucuronidation of 13 flavonoids (7 flavones and 6 flavonols, with hydroxyl groups at C-3, C-4′, C-5, and/or C-7 positions in flavonoid structure) at a substrate concentration

  本研究的目的是确定负责黄酮和黄酮醇葡萄糖醛酸化的重要尿苷二磷酸葡萄糖醛酸转移酶 (UGT) 异构体的区域特异性。我们系统地研究了 13 种黄酮类化合物（7 种黄酮和 6 种黄酮醇，在类黄酮结构的 C-3、C-4'、C-5 和/或 C-7 位具有羟基）在 10 μM 底物浓度下的葡萄糖醛酸化由 8 种重组人 UGT 亚型组成，主要负责黄酮类化合物的代谢，UGT 1A1、1A3、1A6、1A7、1A8、1A9、1A10 和 2B7。在 10 μM 底物浓度下，不同的 UGT 同种型产生不同的区域特异性葡萄糖醛酸化模式。UGT 1A1 葡萄糖醛酸化 3- O（葡萄糖醛酸在 C-3 羟基上取代）、7- O和 4'- O，而 UGT 1A8 和 1A9 优选仅对 3- O和 7- O位进行葡糖醛酸化。UGT 1A1 通常对任何位置的葡萄糖醛酸化没有区域特异性，而 UGT 1A8 和 UGT 1A9 对
• Regioselective Glucuronidation of Flavonols by Six Human UGT1A Isoforms
  作者：Baojian Wu、Beibei Xu、Ming Hu

  DOI：10.1007/s11095-011-0418-5

  日期：2011.8

  Glucuronidation is a major barrier to flavonoid bioavailability; understanding its regiospecificity and reaction kinetics would greatly enhance our ability to model and predict flavonoid disposition. We aimed to determine the regioselective glucuronidation of four model flavonols using six expressed human UGT1A isoforms (UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10). In vitro reaction kinetic profiles of six UGT1A-mediated metabolism of four flavonols (all with 7-OH group) were characterized; kinetic parameters (Km, Vmax and CLint = Vmax/Km) were determined. UGT1A1 and 1A3 regioselectively metabolized the 7-OH group, whereas UGT1A7, 1A8, 1A9 and 1A10 preferred to glucuronidate the 3-OH group. UGT1A1 and 1A9 were the most efficient conjugating enzymes with Km values of ≤1 μM and relative catalytic efficiency ratios of ≥5.5. Glucuronidation by UGT1As displayed surprisingly strong substrate inhibition. In particular, Ksi values (substrate inhibition constant) were less than 5.4 μM for UGT1A1-mediated metabolism. UGT1A isoforms displayed distinct positional preferences between 3-OH and 7-OH of flavonols. Differentiated kinetic properties between 3-O- and 7-O- glucuronidation suggested that (at least) two distinct binding modes within the catalytic domain were possible. The existence of multiple binding modes should provide better “expert” knowledge to model and predict UGT1A-mediated glucuronidation.

  葡萄糖醛酸化是类黄酮生物利用度的主要障碍；了解其区域选择性和反应动力学会大大增强我们建模和预测类黄酮处置的能力。我们的目标是确定四种模型二苯乙烯酮在六种表达的人类UGT1A同工酶（UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10）作用下的区域选择性葡萄糖醛酸化。表征了六种UGT1A介导的四种二苯乙烯酮（均含7-OH基团）的体外反应动力学曲线；确定了动力学参数（Km, Vmax和CLint = Vmax/Km）。UGT1A1和1A3区域选择性地代谢7-OH基团，而UGT1A7, 1A8, 1A9和1A10更倾向于对3-OH基团进行葡萄糖醛酸化。UGT1A1和1A9是最有效的结合酶，其Km值≤1 μM，相对催化效率比≥5.5。UGT1A的葡萄糖醛酸化显示出惊人的强底物抑制作用。特别是，UGT1A1介导的代谢的Ksi值（底物抑制常数）小于5.4 μM。UGT1A同工酶显示出对二苯乙烯酮的3-OH和7-OH的不同位置偏好。3-O-和7-O-葡萄糖醛酸化的区分动力学特性表明（至少）催化域内存在两种不同的结合模式。多种结合模式的存在应提供更好的“专家”知识来建模和预测UGT1A介导的葡萄糖醛酸化。
• Three-Dimensional Quantitative Structure-Activity Relationship Studies on UGT1A9-Mediated 3-O-Glucuronidation of Natural Flavonols Using a Pharmacophore-Based Comparative Molecular Field Analysis Model
  作者：Baojian Wu、John Kenneth Morrow、Rashim Singh、Shuxing Zhang、Ming Hu

  DOI：10.1124/jpet.110.175356

  日期：2011.2

  Glucuronidation is often recognized as one of the rate-determining factors that limit the bioavailability of flavonols. Hence, design and synthesis of more bioavailable flavonols would benefit from the establishment of predictive models of glucuronidation using kinetic parameters [e.g., K m, V max, intrinsic clearance (CLint) = V max/ K m] derived for flavonols. This article aims to construct position (3-OH)-specific comparative molecular field analysis (CoMFA) models to describe UDP-glucuronosyltransferase (UGT) 1A9-mediated glucuronidation of flavonols, which can be used to design poor UGT1A9 substrates. The kinetics of recombinant UGT1A9-mediated 3-O-glucuronidation of 30 flavonols was characterized, and kinetic parameters ( K m, V max, CLint) were obtained. The observed K m, V max, and CLint values of 3-O-glucuronidation ranged from 0.04 to 0.68 μM, 0.04 to 12.95 nmol/mg/min, and 0.06 to 109.60 ml/mg/min, respectively. To model UGT1A9-mediated glucuronidation, 30 flavonols were split into the training (23 compounds) and test (7 compounds) sets. These flavonols were then aligned by mapping the flavonols to specific common feature pharmacophores, which were used to construct CoMFA models of V max and CLint, respectively. The derived CoMFA models possessed good internal and external consistency and showed statistical significance and substantive predictive abilities ( V max model: q 2 = 0.738, r 2 = 0.976, r pred2 = 0.735; CLint model: q 2 = 0.561, r 2 = 0.938, rpred2 = 0.630). The contour maps derived from CoMFA modeling clearly indicate structural characteristics associated with rapid or slow 3-O-glucuronidation. In conclusion, the approach of coupling CoMFA analysis with a pharmacophore-based structural alignment is viable for constructing a predictive model for regiospecific glucuronidation rates of flavonols by UGT1A9.

  葡糖醛酸化通常被认为是限制类黄酮醇生物利用度的决定速率的因素之一。因此，利用类黄酮醇的动力学参数（如 Km、Vmax、内在清除率（CLint）= Vmax/ Km）建立葡糖醛酸化的预测模型，将有利于设计合成更多生物可利用的类黄酮醇。本文旨在构建针对3-OH位点的特定比较分子场分析（CoMFA）模型，描述UDP-葡糖醛酸基转移酶（UGT）1A9介导的类黄酮醇葡糖醛酸化过程，该模型可用于设计不佳的UGT1A9底物。我们对重组UGT1A9介导的30种类黄酮醇的3-O-葡糖醛酸化动力学进行了表征，并获得了动力学参数（Km、Vmax、CLint）。观察到的3-O-葡糖醛酸化Km、Vmax和CLint值分别在0.04至0.68 μM、0.04至12.95 nmol/mg/min和0.06至109.60 ml/mg/min之间。为了模拟UGT1A9介导的葡糖醛酸化，我们将30种类黄酮醇分为训练集（23个化合物）和测试集（7个化合物）。然后通过将类黄酮醇映射到特定的共同特征药效团来对齐，从而构建了Vmax和CLint的CoMFA模型。得到的CoMFA模型具有良好的内在和外在一致性，显示出统计学意义和实质性的预测能力（Vmax模型：q2 = 0.738，r2 = 0.976，rpred2 = 0.735；CLint模型：q2 = 0.561，r2 = 0.938，rpred2 = 0.630）。从CoMFA建模得到的轮廓图清晰地表明了与快速或慢速3-O-葡糖醛酸化相关的结构特征。总之，结合CoMFA分析和基于药效团的结构对齐方法是可行的，可以构建用于UGT1A9介导的类黄酮醇区域特异性葡糖醛酸化速率的预测模型。