hydnocarpin | 51419-48-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 黄酮木脂素
• 英文名称: hydnocarpin
• 英文别名: hydnocarpin D；2-[2,3-Dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-1,4-benzodioxin-6-yl]-5,7-dihydroxy-4h-1-benzopyran-4-one；5,7-dihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]chromen-4-one
• CAS: 51419-48-8
• 化学式: C₂₅H₂₀O₉
• 分子量: 464.428
• InChiKey: ZYWKQKQEAVWKHD-UHFFFAOYSA-N

物化性质

• 沸点：
  740.9±60.0 °C(Predicted)
• 密度：
  1.496±0.06 g/cm3 (20 ºC 760 Torr)
• LogP：
  3.529 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  9

制备方法与用途

(Rac)-Hydnocarpin 是从大风子树中分离出的一种黄酮类化合物，对癌细胞展现出中等程度的细胞毒性。

反应信息

• 作为反应物：
  描述：

  hydnocarpin 在 吡啶 、 盐酸羟胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 36.42h， 生成 3-(6-(5,7-dihydroxy-4-oxo-4H-chromen-2-yl)-3-(4-hydroxy-3-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)-N-(phenylsulfonyl)isoxazole-5-carboxamide
  参考文献：
  名称：

  Exploring Mitochondria-Mediated Intrinsic Apoptosis by New Phytochemical Entities: An Explicit Observation of Cytochrome c Dynamics on Lung and Melanoma Cancer Cells

  摘要：

  Hydnocarpin (Hy) is a flavonoid isolated and purified from the seeds of Hydnocarpus wightiana Blume. Herein, we have developed a built-in semi-synthetic modification on Hy by one-pot multi-component reaction and a [3 + 2] cycloaddition strategy to append five membered isoxazole and isoxazolone as new phytochemical entities (NPCEs). Two selected NPCEs viz Hy-ISO-VIII and Hy-ISO-G from the library of 20 newly synthesized derivatives after in vitro screening unveiled promising cytotoxicity and induced caspase-mediated apoptosis against the human lung and melanoma cancer cells which were well supported by virtual screening based on ligand binding affinity and molecular dynamic simulations. As a new insight, we introduced surface-enhanced Raman spectroscopy to identify the chemo-marker molecular fingerprint to confirm the cellular uptake, cytochrome c release, and DNA fragmentation in a label-free manner. The present findings throw up a surfeit of seminal reasons behind the semi-synthetic modification of Hy, stepping forward to cancer chemotherapy.

  DOI：

  10.1021/acs.jmedchem.9b01098
• 作为产物：
  描述：

  水飞蓟素A,B 在 lithium hydroxide monohydrate 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.0h， 生成 hydnocarpin
  参考文献：
  名称：

  Mitsunobu反应的非常规应用：选择性黄酮木脂素脱水生成羟卡巴汀。

  摘要：

  研究了各种Mitsunobu条件下的一系列黄酮木聚糖（水飞蓟宾A，水飞蓟宾B，异水飞蓟宾A和水飞蓟素A），以实现C-23位置的选择性酯化或一锅反应脱水，从而制得Hydnocarpin D的生物学上重要的对映异构体，hydnocarpin和isohydnocarpin。这代表了以高产率获得这些黄酮木聚糖的唯一的一锅法半合成方法。

  DOI：

  10.3762/bjoc.12.66

文献信息

• Hydnocarpin-Type Flavonolignans: Semisynthesis and Inhibitory Effects on <i>Staphylococcus aureus</i> Biofilm Formation
  作者：Vladimir Vimberg、Marek Kuzma、Eva Stodůlková、Petr Novák、Lucie Bednárová、Miroslav Šulc、Radek Gažák

  DOI：10.1021/acs.jnatprod.5b00430

  日期：2015.8.28

  utilizing this new method. The synthesis is based on the two-step transformation of the readily available flavonolignans from milk thistle (Silybum marianum), accessible by isolation from the commercial extract silymarin. The first step relies on the regioselective formylation of the C-3 hydroxy group of the dihydroflavonol-type precursor using the Vilsmeier–Haack reagent, followed by formic acid elimination

  开发并优化了一种新的，高效的，通用的蛇皮草型黄酮木聚糖半合成法，从而实现了按克规模生产的hydnocarpin D（2）。此外，光学纯的木犀草异构体[（10 R，11 R）-木犀草素（1a），（10 R，11 R）-木犀草素D（2a）和（10 S，11 S）-木犀草素D（2b）的合成）]以及异羟卡巴汀（8）的合成，是首次使用这种新方法实现的。合成基于乳蓟中容易获得的黄酮木聚糖的两步转化（水飞蓟），从商用的提取水飞蓟素隔离访问。第一步依靠使用Vilsmeier-Haack试剂对二氢黄酮型前体的C-3羟基进行区域选择性甲酰化，然后在第二步中用三乙胺消除甲酸。合成的化合物是金黄色葡萄球菌生物膜形成的有效抑制剂，其中（10 S，11 S）-hydnocarpin D（2b）是最有效的抑制剂。此外，测试了葡萄糖对生物膜形成的影响，并且葡萄糖降低了2b的生物膜抑制活性。此外，2b增加了葡萄球菌的敏感性。金黄色
• Exploring Mitochondria-Mediated Intrinsic Apoptosis by New Phytochemical Entities: An Explicit Observation of Cytochrome <i>c</i> Dynamics on Lung and Melanoma Cancer Cells
  作者：Jayadev S. Arya、Manu M. Joseph、Daisy R. Sherin、Jyothi B. Nair、Thanathu K. Manojkumar、Kaustabh K. Maiti

  DOI：10.1021/acs.jmedchem.9b01098

  日期：2019.9.12

  Hydnocarpin (Hy) is a flavonoid isolated and purified from the seeds of Hydnocarpus wightiana Blume. Herein, we have developed a built-in semi-synthetic modification on Hy by one-pot multi-component reaction and a [3 + 2] cycloaddition strategy to append five membered isoxazole and isoxazolone as new phytochemical entities (NPCEs). Two selected NPCEs viz Hy-ISO-VIII and Hy-ISO-G from the library of 20 newly synthesized derivatives after in vitro screening unveiled promising cytotoxicity and induced caspase-mediated apoptosis against the human lung and melanoma cancer cells which were well supported by virtual screening based on ligand binding affinity and molecular dynamic simulations. As a new insight, we introduced surface-enhanced Raman spectroscopy to identify the chemo-marker molecular fingerprint to confirm the cellular uptake, cytochrome c release, and DNA fragmentation in a label-free manner. The present findings throw up a surfeit of seminal reasons behind the semi-synthetic modification of Hy, stepping forward to cancer chemotherapy.
• Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins
  作者：Guozheng Huang、Simon Schramm、Jörg Heilmann、David Biedermann、Vladimír Křen、Michael Decker

  DOI：10.3762/bjoc.12.66

  日期：——

  Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to

  研究了各种Mitsunobu条件下的一系列黄酮木聚糖（水飞蓟宾A，水飞蓟宾B，异水飞蓟宾A和水飞蓟素A），以实现C-23位置的选择性酯化或一锅反应脱水，从而制得Hydnocarpin D的生物学上重要的对映异构体，hydnocarpin和isohydnocarpin。这代表了以高产率获得这些黄酮木聚糖的唯一的一锅法半合成方法。