(4R,5R)-4-hydroxy-5-(1',4',5'-trimethoxynaphth-2'-yl)dihydrofuran-2(3H)-one | 859234-18-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (4R,5R)-4-hydroxy-5-(1',4',5'-trimethoxynaphth-2'-yl)dihydrofuran-2(3H)-one
• 英文别名: (4R,5R)-4-hydroxy-5-(1,4,5-trimethoxynaphthalen-2-yl)dihydrofuran-2(3H)-one；(4R,5R)-4-hydroxy-5-(1,4,5-trimethoxynaphth-2-yl)-dihydrofuran-2(3H)-one；(4R,5R)-4-hydroxy-5-(1,4,5-trimethoxynaphthalen-2-yl)oxolan-2-one
• CAS: 859234-18-7
• 化学式: C₁₇H₁₈O₆
• 分子量: 318.326
• InChiKey: CUKJILGDVCWXLG-PIGZYNQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,5R)-4-hydroxy-5-(1',4',5'-trimethoxynaphth-2'-yl)dihydrofuran-2(3H)-one 在 ammonium cerium(IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 以94%的产率得到5-O-methyljuglomycin
  参考文献：
  名称：

  通过Dötz环化和不对称二羟基化反应对（-）-和（+）-珠霉素A进行高度对映选择性合成

  摘要：

  描述了对-抗生素-（-）-和（+）-珠霉素A的高度对映选择性合成。合成完成了八个步骤，总产率为19％，对映体选择性高（对（-）-珠红霉素A为99.5％[对（+）-珠红霉素A]为98.5％）。合成策略的关键步骤是有效结合Dötz环化反应和不对称二羟基化反应。

  DOI：

  10.1016/j.tetlet.2008.04.059
• 作为产物：
  描述：

  1,5-二羟基萘 在 吡啶 、 sodium dithionite 、 二(三叔丁基膦)钯 、 甲基磺酰胺 、 AD-mix-β 、 N-甲基二环己基胺 、 四丁基溴化铵 、 水 、 碳酸氢钠 、 对甲苯磺酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 62.84h， 生成 (4R,5R)-4-hydroxy-5-(1',4',5'-trimethoxynaphth-2'-yl)dihydrofuran-2(3H)-one
  参考文献：
  名称：

  A Diastereoselective Oxa-Pictet–Spengler-Based Strategy for (+)-Frenolicin B and epi-(+)-Frenolicin B Synthesis

  摘要：

  An efficient diastereoselective oxa-Pictet - Spengler reaction strategy was developed to construct benzoisochroman diastereomers. The utility of the reaction was demonstrated in the context of both the total synthesis of naturally occurring pyranonaphthoquinones (+)-frenolicin B and epi-(+)-frenolicin B as well as a range of frenolicin precursor analogs. The method is versatile and offers exquisite stereocontrol and, as such, offers a synthetic advance for the synthesis of pyranonaphthoquinone analogs.

  DOI：

  10.1021/ol4027649

文献信息

• PYRANONAPHTHOQUINONE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：University of Kentucky Research Foundation

  公开号：US20180055816A1

  公开（公告）日：2018-03-01

  Provided herein are pyranonaphthoquinone compounds and methods of using pyranonaphthoquinone compounds. The method of using the pyranonaphthoquinone compounds includes selectively inhibiting 4E-BP1 phosphorylation by administering at least one pyranonaphthoquinone or pyranonaphthoquinone analog to a subject in need thereof. The pyranonaphthoquinone compounds includes a structure according to Formula I:

  本文提供了吡喃萘醌化合物以及使用吡喃萘醌化合物的方法。使用吡喃萘醌化合物的方法包括通过向需要的受试者施用至少一种吡喃萘醌或吡喃萘醌类似物来选择性地抑制4E-BP1的磷酸化。吡喃萘醌化合物包括符合以下式I的结构：
• Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects
  作者：Qing Ye、Yinan Zhang、Yanan Cao、Xiachang Wang、Yubin Guo、Jing Chen、Jamie Horn、Larissa V. Ponomareva、Luksana Chaiswing、Khaled A. Shaaban、Qiou Wei、Bradley D. Anderson、Daret K. St Clair、Haining Zhu、Markos Leggas、Jon S. Thorson、Qing-Bai She

  DOI：10.1016/j.chembiol.2018.11.013

  日期：2019.3

  tuberous sclerosis complex to inhibit mTORC1/4E-BP1 signaling axis. FB structure-activity relationship studies reveal a positive correlation between inhibition of 4E-BP1 phosphorylation, ROS-mediated cancer cell cytotoxicity, and suppression of tumor growth in vivo. These findings establish FB as the most potent Prx1/Grx3 inhibitor reported to date and also notably highlight 4E-BP1 phosphorylation status

  Peroxiredoxin 1（Prx1）和glutaredoxin 3（Grx3）是两个主要的抗氧化蛋白，在维持氧化还原稳态以促进肿瘤进展中起着关键作用。在这里，我们确定了典型的吡喃并萘醌天然产物贝宁（B）作为通过活性位半胱氨酸的共价修饰的Prx1和Grx3的选择性抑制剂。FB靶向抑制Prx1和Grx3会导致细胞内的谷胱甘肽水平降低，活性氧（ROS）升高以及伴随的癌细胞生长抑制，主要是通过激活与过氧化物酶体结合的结节性硬化复合物来抑制mTORC1 / 4E -BP1信号轴。FB结构-活性关系研究表明抑制4E-BP1磷酸化，ROS介导的癌细胞的细胞毒性和体内肿瘤生长的抑制之间存在正相关。
• Efficient Synthesis of (+)-Kalafungin and (-)-Nanaomycin D by Asymmetric Dihydroxylation, Oxa-Pictet-Spengler Cyclization, and H₂SO₄-Mediated Isomerization
  作者：Reinhard Brückner、Rodney Fernandes

  DOI：10.1055/s-2005-868505

  日期：——

  The pyranonaphthoquinone antibiotics and antitumor agents (+)-kalafungin (1) and (-)-nanaomycin D (3 = ent-1) were synthesized from 1,5-napthalenediol (13) in 11 steps. Stereocontrol was high: 99.5 ee/93% diastereoselectivity for 1, 98.5% ee/94% ­diastereoselectivity for 3. Enantiocontrol was achieved by the asymmetric dihydroxylation of the β,γ-unsaturated ester 9. Dia­stereocontrol was realized in the final step by an almost complete epimerization in H2SO4.

  通过 11 个步骤从 1,5-萘二醇（13）合成了吡喃萘醌类抗生素和抗肿瘤药物 (+)-kalafungin (1) 和 (-)-nanaomycin D (3 = ent-1)。这两种化合物的立体选择性很高：1 的非对映选择性为 99.5%，3 的非对映选择性为 98.5%。δ,δ-不饱和酯 9 的不对称二羟基化实现了对映体控制。在最后一步，通过在 H2SO4 中几乎完全的外延化反应实现了非对映控制。
• A Chiron Approach to the Total Synthesis of (−)-Juglomycin A, (+)-Kalafungin, (+)-Frenolicin B, and (+)-Deoxyfrenolicin
  作者：Rodney A. Fernandes、Vijay P. Chavan、Sandip V. Mulay、Amarender Manchoju

  DOI：10.1021/jo3019939

  日期：2012.11.16

  A general, efficient, and common strategy for the synthesis of (−)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin is reported here. The strategy involves the synthesis of a key building block alkyne from a cheap chiral pool material, d-glucono-δ-lactone, Dötz benzannulation, oxa-Pictet-Spengler reaction, and H2SO4-mediated epimerization.

  此处报道了合成（-）-珠红霉素A，（+）-卡拉芬净，（+）-肾上腺素B和（+）-脱氧肾上腺素的通用，有效且通用的策略。该策略涉及由廉价的手性池材料，d-葡萄糖酸-δ-内酯，Dötz苯环化，oxa-Pictet-Spengler反应和H 2 SO 4介导的差向异构化合成关键的结构单元炔烃。
• A Dötz benzannulation route to the enantioselective synthesis of (−)- and (+)-juglomycin A
  作者：Rodney A. Fernandes、Vijay P. Chavan

  DOI：10.1016/j.tetasy.2011.07.018

  日期：2011.6

  Two synthetic routes based on a Dotz benzannulation toward the enantioselective synthesis of naphthoquinone antibiotics (-)- and (+)-juglomycin A are described. The stereoinducing step is based on asymmetric dihydroxylation. The syntheses are completed in seven to eight steps from Fischer carbene 12. (C) 2011 Elsevier Ltd. All rights reserved.