(2R)-5,7,3',4'-tetramethoxyflavan-3-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (2R)-5,7,3',4'-tetramethoxyflavan-3-one
• 英文别名: 5,7,3',4'-tetramethoxyflavan-3-one；(2R)-5,7,3',4'-tetrakis(methyloxy)flavan-3-one；(2R)-2-(3,4-dimethoxyphenyl)-5,7-dimethoxy-4H-chromen-3-one
• 化学式: C₁₉H₂₀O₆
• 分子量: 344.364
• InChiKey: RTIGUPFEALBBSD-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R)-5,7,3',4'-tetramethoxyflavan-3-one 在 L-Selectride 、 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 以81%的产率得到5,7,3',4'-tetra-O-methylepicatechin
  参考文献：
  名称：

  多酚化学和生物活性研究。2.通过将原花青素B2的O-烷基化衍生物氧化降解为（R）-（-）-2,4-二苯基丁酸，建立黄酮间键合区域和立体化学。

  摘要：

  过去，寡聚原花色素中的黄酮键区域和立体化学的分配依赖于受C环构象影响的经验光谱技术。直到最近，才通过二维NMR方法确定了原花青素B2（3b）的4,8-区域化学。我们在此描述3b中4β-立体化学的证据，方法是将其“顶部”和“底部”表儿茶素部分中带有差异（O-苄基和O-甲基）保护基的衍生物3d氧化降解为（R）-（- ）-2,4-二苯基丁酸。降解过程的关键要素是：（1）通过使用次磷酸作为还原剂的改进的Barton脱氧反应除去C-3醇官能团；（2）通过氢解脱除“顶部”单元的保护基，然后在DMF中与N，N-双（三氟甲磺酰基）苯胺和DBU彻底形成三氟甲磺酸芳基酯；（3）在Pearlman催化剂上“顶部”单元的氢解脱氧，同时伴随着O-C2键的断裂；（4）用NaIO4 / RuCl3选择性氧化“底部”单元。通过（R）-（+）-α-甲基苄基胺盐的X射线晶体结构分析，将迄今未报道的（-）-2，4-二苯基丁酸的

  DOI：

  10.1021/jo000485+
• 作为产物：
  描述：

  儿茶提取物 在 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 7.33h， 生成 (2R)-5,7,3',4'-tetramethoxyflavan-3-one
  参考文献：
  名称：

  多酚化学和生物活性研究。2.通过将原花青素B2的O-烷基化衍生物氧化降解为（R）-（-）-2,4-二苯基丁酸，建立黄酮间键合区域和立体化学。

  摘要：

  过去，寡聚原花色素中的黄酮键区域和立体化学的分配依赖于受C环构象影响的经验光谱技术。直到最近，才通过二维NMR方法确定了原花青素B2（3b）的4,8-区域化学。我们在此描述3b中4β-立体化学的证据，方法是将其“顶部”和“底部”表儿茶素部分中带有差异（O-苄基和O-甲基）保护基的衍生物3d氧化降解为（R）-（- ）-2,4-二苯基丁酸。降解过程的关键要素是：（1）通过使用次磷酸作为还原剂的改进的Barton脱氧反应除去C-3醇官能团；（2）通过氢解脱除“顶部”单元的保护基，然后在DMF中与N，N-双（三氟甲磺酰基）苯胺和DBU彻底形成三氟甲磺酸芳基酯；（3）在Pearlman催化剂上“顶部”单元的氢解脱氧，同时伴随着O-C2键的断裂；（4）用NaIO4 / RuCl3选择性氧化“底部”单元。通过（R）-（+）-α-甲基苄基胺盐的X射线晶体结构分析，将迄今未报道的（-）-2，4-二苯基丁酸的

  DOI：

  10.1021/jo000485+

文献信息

• [EN] METHOD FOR THE PREPARATION OF C-4 COUPLED FLAVONOIDS, PROANTHOCYANIDINS AND ANALOGUES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE FLAVONOÏDES COUPLÉS EN C-4, DE PROANTHOCYANIDINES ET D'ANALOGUES CORRESPONDANTS
  申请人：UNIV FREE STATE ZA

  公开号：WO2009147645A1

  公开（公告）日：2009-12-10

  The invention relates to a novel process for the preparation of C-4 coupled flavonoids, proanthocyanidins and analogues thereof. According to a specific application of the invention, there is provided a method for the preparation of proanthocyanidins and proanthocyanidin analogues.

  这项发明涉及一种新型的制备C-4偶联类黄酮、原花青素及其类似物的方法。根据该发明的一个具体应用，提供了一种制备原花青素和原花青素类似物的方法。
• [EN] SYNTHESIS OF C-3 COUPLED BIFLAVONOIDS AND C-3 COUPLED BIFLAVONOID ANALOGUES<br/>[FR] SYNTHÈSE DE BIFLAVONOÏDES COUPLÉS EN C-3 ET D'ANALOGUES DE BIFLAVONOÏDES COUPLÉS EN C-3
  申请人：UNIV FREE STATE ZA

  公开号：WO2011021167A1

  公开（公告）日：2011-02-24

  The invention relates to methods for the preparation of an optically inactive and optically active compounds which are selected from the group consisting of C-3 coupled biflavonoids and C-3 coupled biflavonoid analogues from a starting material or intermediate which are respectively selected from the group consisting of optically inactive or optically active flavan-3-ols and optically active flavan-3-ones, the method comprising the steps of (a) providing an optically inactive or active compound having a fIavan-3-ol structure or a compound which is a flavan-3-one, (b) if a compound having a flavan-3-ol structure with a hydroxy group on the C-3 carbon is selected as starting material, converting the hydroxy group on the C-3 carbon of the compound having the flavan-3-ol structure to an oxo group to form a flavan-3-one of that compound, (c) providing a compound having a nucleophilic aromatic moiety, which compound is selected from the group of compounds having a nucleophilic aromatic moiety and which have flavonoid base structures and compounds having a nucleophilic aromatic moiety and which do not have a flavonoid base structure, (d) contacting the flavan-3-one provided by step (a) or obtained by step (b) with the compound containing the nucleophilic aromatic moiety in the presence of a Lewis acid; (e) forming a first intermediate compound wherein the oxo group on the C-3 carbon is converted to a hydroxy group by virtue of nucleophilic addition when the compound containing the nucleophilic aromatic moiety is contacted to the C-3 carbon of the flavan-3-one, (f) subjecting the first intermediate compound to dehydration so as to introduce a double bond between the C-3 carbon and C-4 carbon of the intermediate compound with the concomitant removal of the hydroxy group from the C-3 carbon to form an optically active flavene compound which is substituted by the nucleophilic aromatic moiety on the C-3 carbon, (g) optionally subjecting the resultant flavene compound to hydroboration-oxidation hydration thereby removing said double bond between the C-3 carbon and the C-4 carbon with the concomitant introduction of a hydroxy group at the C-4 carbon to form a second intermediate compound, (h) further optionally oxidizing the second intermediate compound of step (g) thereby converting the hydroxy group at the said C-4 carbon to an oxo group, thereby forming a biflavonoid or biflavonoid analogue which is substituted by the selected nucleophilic aromatic moiety on the C-3 carbon, (ι) further optionally, and alternatively to step (h), subjecting the resultant flavene compound of step (f) to OsC4 dihydroxylation thereby removing said double bond between the C-3 carbon and C-4 carbon with the concomitant introduction of a hydroxy group at the C-4 carbon and a hydroxy group at the C-3 carbon to form a third intermediate compound, and (j) subjecting the third intermediate compound to dehydration whereby the hydroxy group at the C-3 carbon is removed and a double bond is introduced between the C-3 carbon and C-4 carbon thereby forming an enol product and allowing such enol product to rearrange spontaneously to form a biflavonoid or biflavonoid analogue having an oxo group at its C-4 carbon and which is substituted by the selected nucleophilic aromatic moiety on its C-3 carbon.

  该发明涉及从起始物质或中间体中选择的光学不活性和光学活性化合物的制备方法，所述化合物选自C-3偶联的双黄酮类和C-3偶联的双黄酮类类似物，所述起始物质或中间体分别选自光学不活性或光学活性的黄酮-3-醇和光学活性的黄酮-3-酮，所述方法包括以下步骤：(a)提供具有黄酮-3-醇结构或为黄酮-3-酮的化合物，该化合物是光学不活性或活性的；(b)如果选择具有C-3碳上羟基的黄酮-3-醇结构的化合物作为起始物质，则将该具有黄酮-3-醇结构的化合物上的C-3碳上的羟基转化为醛基，形成该化合物的黄酮-3-酮；(c)提供具有亲核芳香基团的化合物，所述化合物选自具有亲核芳香基团的化合物和具有黄酮基本结构的化合物以及具有亲核芳香基团的化合物和不具有黄酮基本结构的化合物；(d)在存在Lewis酸的情况下，将步骤(a)提供的或步骤(b)获得的黄酮-3-酮与含有亲核芳香基团的化合物接触；(e)形成第一中间化合物，其中通过亲核加成使含有亲核芳香基团的化合物与黄酮-3-酮的C-3碳接触时，C-3碳上的醛基转化为羟基；(f)将第一中间化合物脱水，以在中间化合物的C-3碳和C-4碳之间引入双键，并同时去除C-3碳上的羟基，形成一种在C-3碳上由亲核芳香基团取代的光学活性黄烯化合物；(g)可选地将所得的黄烯化合物经过氢硼氧化水合反应，从而去除C-3碳和C-4碳之间的双键，并同时在C-4碳引入羟基，形成第二中间化合物；(h)可选地进一步氧化步骤(g)中的第二中间化合物，从而将C-4碳上的羟基转化为醛基，形成在C-3碳上由选定的亲核芳香基团取代的双黄酮或双黄酮类似物；(ι)可选地，作为步骤(h)的替代，将步骤(f)中的所得黄烯化合物经过OsC4双羟基化反应，从而去除C-3碳和C-4碳之间的双键，并同时在C-4碳和C-3碳引入羟基，形成第三中间化合物；(j)将第三中间化合物脱水，从而去除C-3碳上的羟基，并在C-3碳和C-4碳之间引入双键，形成烯醇产物，并使该烯醇产物自发重排，形成在其C-4碳上具有醛基且在其C-3碳上由选定的亲核芳香基团取代的双黄酮或双黄酮类似物。
• Synthesis of C-3 Coupled Biflavonoids and C-3 Coupled Biflavonoid Analogues
  申请人：Van Der Westhuizen Jan Hendrik

  公开号：US20120289715A1

  公开（公告）日：2012-11-15

  The invention relates to methods for the preparation of an optically inactive and optically active compounds which are selected from the group consisting of C-3 coupled biflavonoids and C-3 coupled biflavonoid analogues from a starting material or intermediate which are respectively selected from the group consisting of optically inactive or optically active flavan-3-ols and optically active flavan-3-ones, the method comprising the steps of (a) providing an optically inactive or active compound having a flavan-3-ol structure or a compound which is a flavan-3-one, (b) if a compound having a flavan-3-ol structure with a hydroxy group on the C-3 carbon is selected as starting material, converting the hydroxy group on the C-3 carbon of the compound having the flavan-3-ol structure to an oxo group to form a flavan-3-one of that compound, (c) providing a compound having a nucleophilic aromatic moiety, which compound is selected from the group of compounds having a nucleophilic aromatic moiety and which have flavonoid base structures and compounds having a nucleophilic aromatic moiety and which do not have a flavonoid base structure, (d) contacting the flavan-3-one provided by step (a) or obtained by step (b) with the compound containing the nucleophilic aromatic moiety in the presence of a Lewis acid; (e) forming a first intermediate compound wherein the oxo group on the C-3 carbon is converted to a hydroxy group by virtue of nucleophilic addition when the compound containing the nucleophilic aromatic moiety is contacted to the C-3 carbon of the flavan-3-one, (f) subjecting the first intermediate compound to dehydration so as to introduce a double bond between the C-3 carbon and C-4 carbon of the intermediate compound with the concomitant removal of the hydroxy group from the C-3 carbon to form an optically active flavene compound which is substituted by the nucleophilic aromatic moiety on the C-3 carbon, (g) optionally subjecting the resultant flavene compound to hydroboration-oxidation hydration thereby removing said double bond between the C-3 carbon and the C-4 carbon with the concomitant introduction of a hydroxy group at the C-4 carbon to form a second intermediate compound, (h) further optionally oxidizing the second intermediate compound of step (g) thereby converting the hydroxy group at the said C-4 carbon to an oxo group, thereby forming a biflavonoid or biflavonoid analogue which is substituted by the selected nucleophilic aromatic moiety on the C-3 carbon, (i) further optionally, and alternatively to step (h), subjecting the resultant flavene compound of step (f) to OsO 4 dihydroxylation thereby removing said double bond between the C-3 carbon and C-4 carbon with the concomitant introduction of a hydroxy group at the C-4 carbon and a hydroxy group at the C-3 carbon to form a third intermediate compound, and (j) subjecting the third intermediate compound to dehydration whereby the hydroxy group at the C-3 carbon is removed and a double bond is introduced between the C-3 carbon and C-4 carbon thereby forming an enol product and allowing such enol product to rearrange spontaneously to form a biflavonoid or biflavonoid analogue having an oxo group at its C-4 carbon and which is substituted by the selected nucleophilic aromatic moiety on its C-3 carbon.

  该发明涉及一种从起始物质或中间体中选择的光学不活性和光学活性化合物的制备方法，所述化合物选自C-3偶联的双黄酮类化合物和C-3偶联的双黄酮类似物，所述起始物质或中间体分别选自光学不活性或光学活性的黄酮-3-醇和光学活性的黄酮-3-酮，所述方法包括以下步骤：(a)提供具有黄酮-3-醇结构或为黄酮-3-酮的化合物，该化合物是光学不活性或活性的；(b)如果选择具有C-3碳上羟基的黄酮-3-醇结构化合物作为起始物质，则将具有黄酮-3-醇结构的化合物的C-3碳上的羟基转化为羟基，形成该化合物的黄酮-3-酮；(c)提供具有亲核芳香基团的化合物，所述化合物选自具有亲核芳香基团的化合物和具有黄酮类基本结构的化合物以及具有亲核芳香基团的化合物和不具有黄酮类基本结构的化合物；(d)在存在Lewis酸的情况下，将步骤(a)提供或步骤(b)获得的黄酮-3-酮与含有亲核芳香基团的化合物接触；(e)形成第一中间化合物，其中通过亲核加成使含有亲核芳香基团的化合物与黄酮-3-酮的C-3碳接触时，C-3碳上的羟基转化为羟基；(f)将第一中间化合物脱水，以在中间化合物的C-3碳和C-4碳之间引入双键，并同时去除C-3碳上的羟基，形成由亲核芳香基团取代C-3碳上的光学活性黄烯化合物；(g)可选地将所得的黄烯化合物经过氢硼氧化水合反应，从而去除C-3碳和C-4碳之间的双键，并同时在C-4碳引入羟基，形成第二中间化合物；(h)可选地进一步氧化步骤(g)中的第二中间化合物，将C-4碳上的羟基转化为羟基，从而形成在C-3碳上由所选亲核芳香基团取代的双黄酮或双黄酮类似物；(i)可选地，作为步骤(h)的替代，将步骤(f)中的所得黄烯化合物经过OsO4二羟基化反应，从而去除C-3碳和C-4碳之间的双键，并同时在C-4碳和C-3碳引入羟基，形成第三中间化合物；(j)将第三中间化合物脱水，从而去除C-3碳上的羟基，并在C-3碳和C-4碳之间引入双键，从而形成烯醇产物，并使该烯醇产物自发重排，形成在其C-4碳上具有羟基的双黄酮或双黄酮类似物，并在其C-3碳上由所选亲核芳香基团取代。
• Synthesis of C-3 coupled biflavonoids and C-3 coupled biflavonoid analogues
  申请人：Van Der Westhuizen Jan Hendrik

  公开号：US09296717B2

  公开（公告）日：2016-03-29

  The preparation of C-3 coupled biflavonoids and C-3 coupled biflavonoid analogs occurs from flavan-3-ones that are contacted with a compound having a nucleophilic aromatic moiety, in the presence of a Lewis acid where an intermediate compound is formed with a C-3 hydroxy group. A flavan-3-ol can be converted to a flavan-3-one as required. The intermediate compound is dehydrated to a flavene with a C-3-C-4 double bond. The flavene compound undergoes hydroboration-oxidation hydration to introduce a C-4 hydroxy group that can be oxidized to an oxo group or can be dihydroxylation to introduce hydroxy groups at the C-4 and C-3 carbons and dehydrated to a biflavonoid or biflavonoid analog having an oxo group at its C-4 carbon and substituted by the selected nucleophilic aromatic moiety on its C-3 carbon.

  制备C-3偶联的双黄酮类化合物和C-3偶联的双黄酮类似物的方法是将黄酮-3-酮与带有亲核芳香基团的化合物接触，在路易斯酸的存在下形成一个带有C-3羟基的中间化合物。需要时，黄酮-3-醇可以转化为黄酮-3-酮。中间化合物被脱水成一个带有C-3-C-4双键的黄素。黄素化合物经过氢硼化-氧化水合反应，引入一个C-4羟基，该羟基可以被氧化成一个酮基，或者可以被二羟基化作用引入羟基在C-4和C-3碳上，然后脱水成一个双黄酮或双黄酮类似物，其C-4碳上带有酮基，C-3碳上被所选的亲核芳香基团取代。
• Synthesis of Proanthocyanidins. Part 1. The First Oxidative Formation of the Interflavanyl Bond in Procyanidins
  作者：Matthew C. Achilonu、Susan L. Bonnet、Jan H. van der Westhuizen

  DOI：10.1021/ol801353u

  日期：2008.9.1

  A novel and efficient method for the oxidative condensation of tetra-O-methyl-3-oxocatech in 4 with tetra-O-methylcatechin is described. Treatment of a solution of 3 (2 equiv) and 4 (1 equiv) with silver tetrafluoroborate readily affords the phenolic per-O-methyl ethers of 3-oxocatechin(4-8)-catechin 18 and 19. Subsequent metal hydride reduction provides access to procyanidin B-3 analogues with the 3,4-cis diastereomers predominating.