绣球酚 | 480-47-7

• 物质功能分类: 天然产物 - 香豆素
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 绣球酚
• 英文名称: hydrangenol
• 英文别名: 3-(4'-hydroxyphenyl)-8-hydroxy-3,4-dihydro-2-benzopyran-1-one；(±)-hydrangenol；(+/-)-hydrangenol；hydragenol；3,4-dihydroisocoumarin；8-hydroxy-3-(4-hydroxyphenyl)-3,4-dihydroisochromen-1-one
• CAS: 480-47-7
• 化学式: C₁₅H₁₂O₄
• 分子量: 256.258
• InChiKey: DGKDFNDHPXVXHW-UHFFFAOYSA-N

物化性质

• 熔点：
  181-182 °C(Solv: ethanol (64-17-5))
• 沸点：
  528.3±50.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)
• LogP：
  2.339 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

应用

绣球酚在四氧嘧啶致小鼠糖尿病模型试验中表现出良好的抗糖尿病活性。KK-Ay小鼠服用200mg/（kg·d）的绣球酚后，在两周内血糖和游离脂肪酸水平明显降低；此外，绣球酚还具有良好的抗菌和抗过敏作用。

制备

取500g牛白藤干燥叶粉碎成粗粉，加水提取两次，合并提取液，减压浓缩至密度为1.14（60℃），再加入乙醇使醇浓度达到60%，在0～2℃下冷藏24小时后过滤。滤液再次减压浓缩得到浸膏；将浸膏用甲醇溶解，加入硅胶拌样干燥后进行柱层析分离。经石油醚-乙酸乙酯系统梯度洗脱，并在薄层色谱参考下合并洗脱液，在石油醚-乙酸乙酯（89∶11～87∶13）段中反复重结晶，最终得到白色晶体绣球酚，纯品质量为1.0g。

反应信息

• 作为反应物：
  描述：

  绣球酚 在 sodium tetrahydroborate 、 palladium dichloride 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以99.6%的产率得到半月苔酸
  参考文献：
  名称：

  A 月桂酸的高效制备及二苯乙烯和二氢二苯乙烯衍生物的一些生物活性

  摘要：

  摘要 以硼氢化钠-氯化钯为原料，从绣球花醇中定量得到月桂酸，一种具有休眠诱导、抗真菌、血栓素合成酶和透明质酸酶抑制作用以及植物生长抑制活性的酸。一些由绣球花醇及其苷制备的二苯乙烯和二氢二苯乙烯衍生物也表现出植物生长抑制、透明质酸酶抑制和杀鱼活性。

  DOI：

  10.1016/0031-9422(88)80599-5
• 作为产物：
  描述：

  (3-acetyloxy-2-ethoxycarbonylbenzyl)-triphenylphosphonium bromide 在 palladium on activated charcoal 氢氧化钾 、 氢气 、 sodium ethanolate 、 三氟乙酸 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 53.0h， 生成 绣球酚
  参考文献：
  名称：

  Efficient syntheses of (±)-hydrangenol, (±)-phyllodulcin and (±)-macrophyllol

  摘要：

  In this paper we report on a efficient and flexible synthetic route towards the total syntheses of the dihydrocoumarine derivatives hydrangenol (1), phyllodulcin (1a) and macrophyllol (6b). The syntheses started with a readily available phosphonium salt 2 and suitable modified benzaldehydes 3/3a/3b resulting in 46 to 61% overall yields in three to four-steps sequences. The racemic products could be separated by chiral HPLC. The evidence of the(R)-enantiomer for sweetness could be demonstrated for la. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.09.046

文献信息

• Directed metalation of tertiary benzamides.
  作者：M. Wanatabe、M. Sahara、S. Furukawa、R. Billedeau、V. Snieckus

  DOI：10.1016/s0040-4039(00)87180-4

  日期：1982.1

  Brief syntheses of isocoumarin natural products hydrangenol () and phyllodulcin () via ortho-lithiated benzamide intermediates are described.

  描述了通过邻位锂化的苯甲酰胺中间体简短合成异香豆素天然产物hydrangenol（）和phyllodulcin（）。
• Synthesis of 3-substituted 8-hydroxy-3,4-dihydroisocoumarins via successive lateral and ortho-lithiations of 4,4-dimethyl-2-(o-tolyl)oxazoline
  作者：Naruki Tahara、Tsutomu Fukuda、Masatomo Iwao

  DOI：10.1016/j.tetlet.2004.04.158

  日期：2004.6

  of 4,4-dimethyl-2-(o-tolyl)oxazoline in THF with sec-BuLi, aromatic or aliphatic aldehydes, sec-BuLi, B(OMe)3, and H2O2 produced the laterally alkylated and ortho-hydroxylated oxazolines in one-pot. Treatment of these products with TFA in aqueous THF provided 3-substituted 8-hydroxy-3,4-dihydroisocoumarins in 44–75% overall yields. This procedure allowed the short synthesis of (±)-hydrangenol and (±)-phyllodulcin

  用仲-BuLi，芳族或脂族醛，仲-BuLi，B（OMe）3和H 2 O 2依次处理THF中的4,4-二甲基-2-（邻甲苯基）恶唑啉，生成侧烷基化和邻位一锅中的-羟基化的恶唑啉。用TFA在THF水溶液中处理这些产品可提供3-取代的8-羟基-3,4-二氢异香豆素，总产率为44-75％。该方法允许短合成（±）-羟基和（±）-叶绿素，它们是天然存在的具有药理学意义的3,4-二氢异香豆素。还描述了通过三阴离子中间体更经济地合成（±）-叶绿素。
• Development of Bioactive Functions in Hydrangeae Dulcis Folium. VI. Syntheses of Thunberginols A and F and Their 3'-Deoxy-Derivatives Using Regiospecific Lactonization of Stilbene Carboxylic Acid: Structures and Inhibitory Activity on Histamine Release of Hydramacrophyllols A and B.
  作者：Masayuki YOSHIKAWA、Hiromi SHIMADA、Nobuhiro YAGI、Nobutoshi MURAKAMI、Hiroshi SHIMODA、Johji YAMAHARA、Hisashi MATSUDA

  DOI：10.1248/cpb.44.1890

  日期：——

  Lactonization reaction of 2-carboxystilbene mediated by copper(II) chloride proceeded regiospecifically to give the five-membered lactone, while the bromolactonizations using N-bromosuccinimide and anodic oxidation were found to furnish the six-membered lactone. Using these regiospecific lactonization reactions as a key step, antiallergic and antimicrobial isocoumarins and the benzylidenephthalides thunberginols A and F and their 3'-deoxyanalogs were synthesized from phyllodulcin and hydrangenol.Two phthalides called hydramacrophyllols A and B were isolated from Hydrangeae Dulcis Folium and their stereostructures were determined on the basis of physicochemical and chemical evidence, which included the syntheses of hydramacrophyllols A and B from hydrangenol by the application of the lactonization method using copper(II)chloride. In addition, hydramacrophyllols A and B were found to exhibit an inhibitory effect on the histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.

  氯化铜（II）介导的 2-羧基二苯乙烯的内酯化反应进行了区域特异性反应，生成了五元内酯，而使用 N-溴代琥珀酰亚胺和阳极氧化进行的溴内酯化反应则生成了六元内酯。利用这些区域特异性内酯化反应作为关键步骤，从phyllodulcin 和 hydrangenol 合成了抗过敏和抗菌的异香豆素和苯亚甲基酞thunberginols A 和 F 及其 3'-deoxyanalogs 。根据物理化学和化学证据，从绣线菊叶中分离出了两种名为水飞蓟醇 A 和 B 的邻苯二甲酸盐，并确定了它们的立体结构，其中包括应用氯化铜（II）内酯化法从水飞蓟醇合成了水飞蓟醇 A 和 B。此外，还发现水合麦考酚 A 和 B 对抗原-抗体反应诱导的大鼠腹腔渗出细胞释放组胺具有抑制作用。
• Chemical Transformation from Dihydroisocoumarin into Benzylidenephthalide by Use of Regiospecific Oxidative Lactonization Mediated by Copper Chloride(II). Syntheses of Thunberginol F and Hydramacrophyllol A and B.
  作者：Masayuki YOSHIKAWA、Emiko HARADA、Nobuhiro YAGI、Yasuhiro OKUNO、Osamu MURAOKA、Hiroshi AOYAMA、Nobutoshi MURAKAMI

  DOI：10.1248/cpb.42.721

  日期：——

  Oxidative lactonization of 2-carboxystilbene mediated by CuCl2 proceeded regiospecifically to give the five-membered lactone. By utilizing this lactonization as a key reaction, chemical transformation from dihydroisocoumarine into benzylidenephthalide was accomplished, and it was applied to structural elucidation of two new phthalide, hydramacrophyllols A and B.

  CuCl2 介导的 2-羧基二苯乙烯的氧化内酯化反应进行区域特异性，得到五元内酯。利用该内酯化反应作为关键反应，完成了从二氢异香豆素到亚苄基苯酞的化学转化，并将其应用于两种新的苯酞——Hydrmacrophyllols A和B的结构解析。
• Antifungal activity of oosponol, oospolactone, phyllodulcin, hydrangenol, and some other related compounds.
  作者：KOOHEI NOZAWA、MIKIKO YAMADA、YOSHIKO TSUDA、KENICHI KAWAI、SHOICHI NAKAJIMA

  DOI：10.1248/cpb.29.2689

  日期：——

  Various natural 8-hydroxyisocoumarin derivatives, i.e., oosponol (1), oospolactone (2), d-phyllodulcin (d-4) and dl-hydrangenol (dl-5), were examined for antifungal activity. Several derivatives of d-4 and dl-5 were also examined. It is very interesting that d-phyllodulcin, a sweetening component of Hydrangea serrata SERINGE var. thunbergii (Japanese name amacha), was found to possess antifungal activity.

  对各种天然8-羟基异香豆素衍生物，即卵形醇（1）、卵形内酯（2）、d-叶状杜鹃素（d-4）和dl-绣球醇（dl-5）进行了抗真菌活性测试。此外，还对d-4和dl-5的几种衍生物进行了测试。非常有趣的是，d-叶状杜鹃素是一种绣球花（Hydrangea serrata SERINGE var. thunbergii）的甜味成分，被发现具有抗真菌活性。