methyl-2,2-dimethyl-3-hydroxy-3-(4-hydroxyphenyl)-propionate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl-2,2-dimethyl-3-hydroxy-3-(4-hydroxyphenyl)-propionate
• 英文别名: methyl 3-hydroxy-(4-hydroxyphenyl)-2,2-dimethylpropanoate；Methyl 3-hydroxy-3-(4-hydroxyphenyl)-2,2-dimethylpropanoate
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: PSIZPSWBMCEVKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-萘硼酸 、 methyl-2,2-dimethyl-3-hydroxy-3-(4-hydroxyphenyl)-propionate 在 copper diacetate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以40%的产率得到methyl 3-hydroxy-2,2-dimethyl-3-(4-(naphthalene-2-yloxy)phenyl)propanoate
  参考文献：
  名称：

  维甲酸4-羟化酶（CYP26）的小分子抑制剂：咪唑3-（4-（芳基-2-基氨基）苯基）丙酸甲酯的合成及生物评价

  摘要：

  描述了新型咪唑甲基3-（4-（芳基-2-基氨基）苯基）丙酸酯在MCF-7 CYP26A1微粒体测定中的合成和强抑制活性。CYP26A1 mRNA的诱导用于评估化合物增强类视黄醇反应性神经母细胞瘤细胞系中全反式视黄酸（ATRA）的生物学效应的能力。最有希望的抑制剂3-咪唑-1-基-2-甲基-3- [4-（萘-2-基氨基）-苯基]-丙酸甲酯（20），IC 50为3 nM（相比用利阿罗唑IC 50 540纳米和R116010 IC 50为10nM）中的溶液用于CYP选择性使用CYP酶，致突变性（艾姆斯画面），和肝稳定性的面板进一步评估。

  DOI：

  10.1021/jm101583w
• 作为产物：
  描述：

  2-溴代异丁酸甲酯 、 2-(4-hydroxyphenyl)-1,3-dioxalane sodium salt 以44%的产率得到methyl-2,2-dimethyl-3-hydroxy-3-(4-hydroxyphenyl)-propionate
  参考文献：
  名称：

  Chromium-mediated aldol and homoaldol reactions on solid support directed towards an iterative polyol strategy

  摘要：

  Chromiumn-Reformatsky and chromium-homoaldol reactions run Under neutral and mild reaction conditions. They are highly chemoselective, tolerant towards most common functional groups, and are not prone to retroaldol reactions. Initial studies directed to transfer these homogeneous chromium-mediated solution-phase reactions to solid phase are presented. The main objective was to develop a methodology to aid a combinatorial iterative strategy to polyols (polyketides) on solid phase. A general reactivity problem was observed with polystyrene based resins compared to the solution-phase reactions, independent if the electrophilic (aldehyde) or nucleophilic (bromide) end of the polyol chain was supported to the resin. A complicated penetration, or loss of the polar solvent environment after penetration into the resin, might be responsible for the reduced reactivity. Application of either a soluble polystyrene resin or a polystyrene resin with a polar polyethylene glycol tether resulted in improved yields. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.10.038

文献信息

• Practical aldol reaction of trimethylsilyl enolate with aldehyde catalyzed by N-methylimidazole as a Lewis base catalyst
  作者：Hisahiro Hagiwara、Hideyuki Inoguchi、Masakazu Fukushima、Takashi Hoshi、Toshio Suzuki

  DOI：10.1016/j.tetlet.2006.05.074

  日期：2006.7

  Aldol reaction of trimethylsilyl enolate with aldehyde proceeded in the presence of a catalytic amount of a Lewis base, N-methylimidazole, and lithium chloride in DMF at room temperature. Not only aryl aldehyde but also alkyl aldehyde provided the aldol product in satisfactory yields. The reaction was mild enough to apply to the aldehyde having HO, AcO, THPO, TBDMSO, MeS, pyridyl or olefinic group

  在室温下，在DMF中在催化量的路易斯碱，N-甲基咪唑和氯化锂的存在下，进行烯丙基三甲基甲硅烷基酯与醛的醛醇缩合反应。不仅芳基醛而且烷基醛都以令人满意的产率提供了羟醛产物。该反应足够温和以适用于具有HO，AcO，THPO，TBDMSO，MeS，吡啶基或烯基的醛。微波辐射加速了反应。
• Aldol Reaction of Trimethylsilyl Enolate with Aldehyde Catalyzed by Pyridine<i>N</i>-Oxide as a Lewis Base Catalyst
  作者：Hisahiro Hagiwara、Hideyuki Inoguchi、Masakazu Fukushima、Takashi Hoshi、Toshio Suzuki

  DOI：10.1055/s-2005-872664

  日期：——

  Aldol reaction of trimethylsilyl enolate with aldehydes proceeded in the presence of a catalytic amount of a Lewis base, pyridine N-oxide, and lithium chloride in DMF at room temperature. Not only aryl aldehydes but also alkyl aldehydes provided the aldol products in satisfactory yields. The reaction was mild enough to apply to aldehydes having HO, AcO, THPO, TBDMSO, MeS, pyridyl, or olefinic groups

  三甲基甲硅烷基烯醇酯与醛的羟醛反应在催化量的路易斯碱、吡啶N-氧化物和氯化锂的存在下在DMF中在室温下进行。不仅芳基醛而且烷基醛都以令人满意的产率提供醛醇产物。该反应足够温和以适用于具有 H2O、AcO、THPO、TBDMSO、MeS、吡啶基或烯烃基团的醛。
• [EN] CYP26 INHIBITORS<br/>[FR] INHIBITEURS DE CYP26
  申请人：CANCER REC TECH LTD

  公开号：WO2009153566A1

  公开（公告）日：2009-12-23

  A compound of formula (I) wherein X is selected from O, S, NH or CH2; Rd and Rp are optional naphthyl group substituents; RHet is imidazolyl, triazolyl or pyridyl; and Rc is C1-4 alkyl substituted by a group selected from: hydroxy, amino, amido, carboxy, C1-7 alkyl ester, C5-7 aryl-C1-2 alkyl ester, sulfonamino, sulfinamino, hydroxamino and tetrazolyl.

  公式（I）的化合物，其中X选择自O、S、NH或CH2；Rd和Rp是可选的萘基取代物；RHet是咪唑基、三唑基或吡啶基；Rc是C1-4烷基，通过选择的基团取代，包括：羟基、氨基、酰胺基、羧基、C1-7烷基酯、C5-7芳基-C1-2烷基酯、磺胺基、亚砜胺基、羟胺基和四唑基。
• Self-promoted Aldol Reaction between Aldehyde Having Lewis Base Moiety and Trimethylsilyl Enolate
  作者：Takashi Nakagawa、Hidehiko Fujisawa、Teruaki Mukaiyama

  DOI：10.1246/cl.2004.92

  日期：2004.2

  Self-promoted aldol reaction between aldehydes having Lewis base moieties and trimethylsilyl enolates proceeded smoothly to afford the corresponding aldols in good to high yields. It is noted that various functionalized aldols can be directly obtained without protection of functional groups in the above reaction.

  具有路易斯碱部分的醛与三甲基甲硅烷基烯醇化物之间的自促进醛醇反应顺利进行，以良好到高产率提供相应的醛醇。需要说明的是，上述反应可以直接得到各种功能化的羟醛，无需对官能团进行保护。
• Chromium-mediated aldol and homoaldol reactions on solid support directed towards an iterative polyol strategy
  作者：Ludger A. Wessjohann、Harry Wild、Henri S. Schrekker

  DOI：10.1016/j.tetlet.2004.10.038

  日期：2004.11

  Chromiumn-Reformatsky and chromium-homoaldol reactions run Under neutral and mild reaction conditions. They are highly chemoselective, tolerant towards most common functional groups, and are not prone to retroaldol reactions. Initial studies directed to transfer these homogeneous chromium-mediated solution-phase reactions to solid phase are presented. The main objective was to develop a methodology to aid a combinatorial iterative strategy to polyols (polyketides) on solid phase. A general reactivity problem was observed with polystyrene based resins compared to the solution-phase reactions, independent if the electrophilic (aldehyde) or nucleophilic (bromide) end of the polyol chain was supported to the resin. A complicated penetration, or loss of the polar solvent environment after penetration into the resin, might be responsible for the reduced reactivity. Application of either a soluble polystyrene resin or a polystyrene resin with a polar polyethylene glycol tether resulted in improved yields. (C) 2004 Elsevier Ltd. All rights reserved.