2,2-dimethyl-4H-naphtho[2,3-d][1,3]dioxin-4-one | 1410797-84-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,2-dimethyl-4H-naphtho[2,3-d][1,3]dioxin-4-one
• 英文别名: 2,2-Dimethyl-4H-naphtho[2,3-d][1,3]dioxin-4-one；2,2-dimethylbenzo[g][1,3]benzodioxin-4-one
• CAS: 1410797-84-0
• 化学式: C₁₄H₁₂O₃
• 分子量: 228.247
• InChiKey: XAXHCOSUUPSWQL-UHFFFAOYSA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  417.9±34.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  17.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-氨基吡啶 、 2,2-dimethyl-4H-naphtho[2,3-d][1,3]dioxin-4-one 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以87%的产率得到3-羟基-N-2-吡啶-2-萘胺
  参考文献：
  名称：

  Structure–activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription

  摘要：

  CREB (cyclic AMP-response element binding protein) is a downstream transcription factor of a multitude of signaling pathways emanating from receptor tyrosine kinases or G-protein coupled receptors. CREB is not activated until it is phosphorylated at Ser133 and its subsequent binding to CREB-binding protein (CBP) through kinase-inducible domain (KID) in CREB and KID-interacting (KIX) domain in CBP. Tumor tissues from various organs present higher level of expression and activation of CREB. Thus CREB has been proposed as a promising cancer drug target. We previously described naphthol AS-E (1a) as a small molecule inhibitor of CREB-mediated gene transcription in living cells. Here we report the structure-activity relationship (SAR) studies of la by modifying the appendant phenyl ring. All the compounds were evaluated for in vitro inhibition of KIX-KID interaction, cellular inhibition of CREB-mediated gene transcription and inhibition of proliferation of four cancer cell lines (A549, MCF-7, MDA-MB-231 and MDA-MB-468). SAR indicated that a small and electron-withdrawing group was preferred at the para-position for KIX-KID interaction inhibition. Compound la was selected for further biological characterization and it was found that la down-regulated the expression of endogenous CREB target genes. Expression of a constitutively active CREB mutant, VP16-CREB in MCF-7 cells rendered the cells resistant to la, suggesting that CREB was critical in mediating its anticancer activity. Furthermore, la was not toxic to normal human cells. Collectively, these data support that la represents a structural template for further development into potential cancer therapeutics with a novel mechanism of action. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.056
• 作为产物：
  描述：

  乙基3-羟基-2-萘甲酸酯 在 potassium dithionate 、 四乙基溴化铵 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 0.67h， 生成 2,2-dimethyl-4H-naphtho[2,3-d][1,3]dioxin-4-one
  参考文献：
  名称：

  通过醚和硫醚的 α-Csp3-H 活化实现无过渡金属的脱氢环化

  摘要：

  我们在此报道了四乙基溴化铵催化 O- 或 S- 烷基化水杨酸或硫代水杨酸衍生物的分子内氧化环化以获得 4 H -苯并[ d ] [1,3] 二恶英-4-酮或 4 H -苯并[ d ] [ 1,3]oxathiin-4-ones，分别。水杨酸衍生物的氧化环化在 110 °C 通过自由基途径进行。相反，硫代水杨酸的环化在室温下通过离子途径顺利进行。值得注意的是，整体反应速度快，反应时间短，产品收率高，季碳中心形成顺利。

  DOI：

  10.1055/a-2017-6065

文献信息

• Nucleophilic Addition Reaction with Dearomatization of Naphthalene Ring
  作者：Hirotaka Sasaki、Kotaro Kiyotaki、Ayumi Imayoshi、Kazunori Tsubaki

  DOI：10.1248/cpb.c19-01117

  日期：2020.4.1

  Various aromatic lactones have been synthesized and their regioselectivity (1,2-addition vs. 1,4- or 1,6-addition) investigated in reactions with organolithium species, particularly n-BuLi and sec-BuLi. The regioselectivity varied greatly depending on various factors, such as the bulkiness of both substrates and organolithium species, and types of solvent and cosolvent. In particular, 1,4-addition with dearomatization occurred preferentially using sec-BuLi as the nucleophile in tetrahydrofuran (THF) with hexamethylphosphoramide (HMPA) or N,N′-dimethylpropyleneurea (DMPU) as cosolvent. For sec-BuLi, the reaction was estimated to proceed through a single-electron transfer mechanism.

  我们合成了各种芳香族内酯，并研究了它们在与有机锂（尤其是正-BuLi 和仲-BuLi）反应时的区域选择性（1,2-加成与 1,4- 或 1,6- 加成）。反应的区域选择性因各种因素（如底物和有机锂的体积、溶剂和助溶剂的类型）的不同而有很大差异。特别是，在以六甲基磷酰胺（HMPA）或 N,N′-二甲基丙烯脲（DMPU）为共溶剂的四氢呋喃（THF）中，以仲丁锂为亲核体的 1,4-加成脱芳香化反应优先发生。对于仲丁基锂，估计反应是通过单电子转移机制进行的。
• Reactions of Quino-Ketenes with C-Nucleophiles: Syntheses of (2-Hydroxyphenyl)methanols and 2<i>-</i>Hydroxyphenyl Ketones
  作者：Hande Gündüz、Volkan Kumbaraci、Naciye Talinli

  DOI：10.1002/hlca.201300391

  日期：2014.8

  In this study, we have developed a new, efficient, and one‐step protocol for the synthesis of derivatives of 2,4‐dihydroxyphenyl ketones and/or 2,4‐dihydroxyphenyl/naphthalenyl methanols starting from benzodioxinones/naphthodioxinones and organolithium compounds. Reactions have been performed under thermal conditions without catalyst. This work is the first example of the preparation of these products

  在这项研究中，我们开发了一种新的，高效的，一步一步的方法，用于从苯并二恶英酮/萘二恶英酮和有机锂化合物开始合成2,4-二羟基苯基酮和/或2,4-二羟基苯基/萘甲醇的衍生物。反应是在没有催化剂的热条件下进行的。这项工作是从2-羟基酸开始制备这些产品的第一个例子。