1,1-双(3-甲基噻吩-2-基)丁烷-1,4-二醇 | 847233-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 中文名称: 1,1-双(3-甲基噻吩-2-基)丁烷-1,4-二醇
• 英文名称: 1,1-bis(3-methyl-2-thienyl)butane-1,4-diol
• 英文别名: 1,1-bis(3-methylthiophen-2-yl)butane-1,4-diol
• CAS: 847233-26-5
• 化学式: C₁₄H₁₈O₂S₂
• 分子量: 282.428
• InChiKey: HAHLNYYNXFHQOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  473.1±45.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  96.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-双(3-甲基噻吩-2-基)丁烷-1,4-二醇 在 盐酸 、 C₆₃H₇₈IrNOP⁽²⁺⁾*C₃₂H₁₂BF₂₄^(1-) 、 氢气 、 potassium carbonate 、 三乙胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 水 、 丙酮 为溶剂， 1.0~60.0 ℃ 、607.99 kPa 条件下， 反应 135.0h， 生成 噻加宾
  参考文献：
  名称：

  铱催化不饱和杂环酸的对映选择性加氢

  摘要：

  螺旋结合：一种高度对映选择性的不饱和杂环羧酸的加氢已经通过使用手性铱/ spirophosphino恶唑啉催化剂开发（参见方案; BAR ˚F - =四[3,5-双（三氟甲基）苯基]硼酸盐，的Boc =叔丁氧羰基） 。该反应提供了制备具有优异对映选择性的旋光杂环酸的有效方法。

  DOI：

  10.1002/anie.201301341
• 作为产物：
  描述：

  γ-丁内酯 、 2-溴-3-甲基噻吩 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 以89 %的产率得到1,1-双(3-甲基噻吩-2-基)丁烷-1,4-二醇
  参考文献：
  名称：

  (R)-噻加宾的对映选择性合成通过不对称氢原子转移协议

  摘要：

  利用不对称氢原子转移方案构建其必需的手性叔碳中心，实现了噻加宾的对映选择性合成。通过双 N-取代的环化反应被巧妙地安排为安装关键生物碱环的另一个关键步骤。与以往使用市售烟酸酯作为起始原料以确保合成路线短的合成策略相比，该策略使用易于修饰和易于获得的烷基取代丙烯酸酯作为起始原料，从而为类似物的简便合成提供了方案和 tiagabine 的衍生物用于进一步的生物学研究。

  DOI：

  10.1055/a-2039-6180

文献信息

• Ring-chain tautomerism in 2,2-bis(2-thienyl)tetrahydrofurans: preparation of [butene-2H5]-tiagabine
  作者：John M. Herbert、Trevor W. Mathers

  DOI：10.1002/jlcr.1787

  日期：2010.7

  A concise preparation of [butene-2H5]-tiagabine hydrochloride starting from [2H6]-γ-butyrolactone is described. It was necessary to ring-open the labeled γ-butyrolactone precursor before the addition of 2-thienyllithium to avoid cyclisation of the intermediate to a 2,2-bis(2-thienyl)tetrahydrofuran. Copyright © 2010 John Wiley & Sons, Ltd.

  描述了从 [2H6]-γ-丁内酯开始的 [丁烯-2H5]-tiagabine 盐酸盐的简明制备。有必要在添加 2-噻吩基锂之前将标记的 γ-丁内酯前体开环，以避免中间体环化为 2,2-双（2-噻吩基）四氢呋喃。版权所有 © 2010 John Wiley & Sons, Ltd.
• Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues
  作者：Rasmus P. Clausen、Ejner K. Moltzen、Jens Perregaard、Sibylle M. Lenz、Connie Sanchez、Erik Falch、Bente Frølund、Tina Bolvig、Alan Sarup、Orla M. Larsson、Arne Schousboe、Povl Krogsgaard-Larsen

  DOI：10.1016/j.bmc.2004.10.029

  日期：2005.2

  A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-4-en-yl)amino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (17a, IC50 = 0.14 muM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability. (C) 2004 Elsevier Ltd. All rights reserved.
• Iridium-Catalyzed Enantioselective Hydrogenation of Unsaturated Heterocyclic Acids
  作者：Song Song、Shou-Fei Zhu、Liu-Yang Pu、Qi-Lin Zhou

  DOI：10.1002/anie.201301341

  日期：2013.6.3

  binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF−=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate, Boc=tert‐butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities.

  螺旋结合：一种高度对映选择性的不饱和杂环羧酸的加氢已经通过使用手性铱/ spirophosphino恶唑啉催化剂开发（参见方案; BAR ˚F - =四[3,5-双（三氟甲基）苯基]硼酸盐，的Boc =叔丁氧羰基） 。该反应提供了制备具有优异对映选择性的旋光杂环酸的有效方法。
• Enantioselective Synthesis of (R)-Tiagabine via Asymmetric Hydrogen Atom Transfer Protocol
  作者：Jie Jiang、Yong-Qiang Zhang、Longfei Li、Wanjiao Chen、Zhongyun Xu

  DOI：10.1055/a-2039-6180

  日期：——

  An enantioselective synthesis of tiagabine has been achieved utilizing an asymmetric hydrogen atom transfer protocol to construct its essential chiral tertiary carbon center. A cyclization reaction via double N-substitution is tactically orchestrated as the other key step to install the crucial alkaloid ring. Compared with the previous synthetic strategy, which used commercially available nicotinate

  利用不对称氢原子转移方案构建其必需的手性叔碳中心，实现了噻加宾的对映选择性合成。通过双 N-取代的环化反应被巧妙地安排为安装关键生物碱环的另一个关键步骤。与以往使用市售烟酸酯作为起始原料以确保合成路线短的合成策略相比，该策略使用易于修饰和易于获得的烷基取代丙烯酸酯作为起始原料，从而为类似物的简便合成提供了方案和 tiagabine 的衍生物用于进一步的生物学研究。