(1S)-2-氯-1-(3-氯苯基)乙醇 | 174699-78-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (1S)-2-氯-1-(3-氯苯基)乙醇
• 英文名称: (S)-2-chloro-1-(3-chlorophenyl)-ethanol
• 英文别名: (S)-2-chloro-1-(3-chlorophenyl)ethanol；(S)-2-chloro-1-(m-chlorophenyl)ethanol；2-chloro-1-(3'-chlorophenyl)ethanol；2-chloro-1-(3-chlorophenyl)ethanol；(S)-CCE；(S)-2-Chloro-1-(3-chloro-phenyl)-ethanol；(1S)-2-chloro-1-(3-chlorophenyl)ethanol
• CAS: 174699-78-6
• 化学式: C₈H₈Cl₂O
• 分子量: 191.057
• InChiKey: LBSKQOSGSUKVDG-MRVPVSSYSA-N

物化性质

• 沸点：
  284.6±25.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1S)-2-氯-1-(3-氯苯基)乙醇 在 盐酸 、 氨 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 120.0h， 生成 胰岛素样生长因子-1 受体拮抗剂
  参考文献：
  名称：

  Discovery of a 1H-Benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) Inhibitor of Insulin-like Growth Factor I Receptor Kinase with in Vivo Antitumor Activity

  摘要：

  Compound 3 (BMS-536924), a novel small-molecule inhibitor of the insulin-like growth factor receptor kinase with equal potency against the insulin receptor is described. The in vitro and in vivo biological activity of this interesting compound is also reported.

  DOI：

  10.1021/jm050392q
• 作为产物：
  描述：

  3-氯苯乙酮 在 磺酰氯 、 (OCOCF3)>2 、 氢气 作用下， 以 甲苯 为溶剂， 20.0 ℃ 、5.0 MPa 条件下， 反应 48.0h， 生成 (1S)-2-氯-1-(3-氯苯基)乙醇
  参考文献：
  名称：

  使用对映选择性加氢选择性合成手性非典型β-肾上腺素苯基乙醇氨基四氢呋喃激动剂SR58611A

  摘要：

  我们已经开发出非典型的β-肾上腺素苯基乙醇氨基四氢呋喃激动剂SR58611A的另一种合成方法。已合成了两种关键中间体，涉及对氨基酮和烯酰胺的对映选择性氢化，分别提供了> 96％ee和> 98％ee的相应氨基醇和酰胺。

  DOI：

  10.1016/s0040-4039(99)00807-2

文献信息

• Purification and Characterization of an NADH-Dependent Alcohol Dehydrogenase from<i>Candida maris</i>for the Synthesis of Optically Active 1-(Pyridyl)ethanol Derivatives
  作者：Shigeru KAWANO、Miho YANO、Junzo HASEGAWA、Yoshihiko YASOHARA

  DOI：10.1271/bbb.100528

  日期：2011.6.23

  A novel (R)-specific alcohol dehydrogenase (AFPDH) produced by Candida maris IFO10003 was purified to homogeneity by ammonium sulfate fractionation, DEAE-Toyopearl, and Phenyl-Toyopearl, and characterized. The relative molecular mass of the native enzyme was found to be 59,900 by gel filtration, and that of the subunit was estimated to be 28,900 on SDS-polyacrylamide gel electrophoresis. These results suggest that the enzyme is a homodimer. It required NADH as a cofactor and reduced various kinds of carbonyl compounds, including ketones and aldehydes. AFPDH reduced acetylpyridine derivatives, β-keto esters, and some ketone compounds with high enantioselectivity. This is the first report of an NADH-dependent, highly enantioselective (R)-specific alcohol dehydrogenase isolated from a yeast. AFPDH is a very useful enzyme for the preparation of various kinds of chiral alcohols.

  一种由Candida maris IFO10003产生的新型（R）-特异性醇脱氢酶（AFPDH）通过硫酸铵分级、DEAE-Toyopearl和Phenyl-Toyopearl纯化至均一，并进行了表征。通过凝胶过滤法测得该酶的原分子质量为59,900，而在SDS-聚丙烯酰胺凝胶电泳中亚基的估计分子质量为28,900。这些结果表明该酶为同源二聚体。它需要NADH作为辅因子，并能还原包括酮和醛在内的多种羰基化合物。AFPDH能高对映选择性地还原乙酰吡啶衍生物、β-酮酯和某些酮化合物。这是首例从酵母中分离出的依赖NADH的高对映选择性（R）-特异性醇脱氢酶的报道。AFPDH对于制备多种手性醇是非常有用的酶。
• Practical Synthesis of Optically Active Styrene Oxides via Reductive Transformation of 2-Chloroacetophenones with Chiral Rhodium Catalysts
  作者：Takayuki Hamada、Takayoshi Torii、Kunisuke Izawa、Ryoji Noyori、Takao Ikariya

  DOI：10.1021/ol020213o

  日期：2002.11.1

  [reaction: see text] A practical method for the synthesis of optically active styrene oxides has been developed via formation of optically active 2-chloro-1-phenylethanols generated by reductive transformation of ring-substituted 2-chloroacetophenones. The optically active alcohols with up to 98% ee are obtainable from the asymmetric reduction of acetophenones with an S/C = 1000-5000 with a formic

  [反应：见正文]通过形成由环取代的2-氯苯乙酮的还原转化而生成的光学活性的2-氯-1-苯基乙醇，已经开发了一种合成光学活性的苯乙烯氧化物的实用方法。ee高达98％的旋光性醇可通过将S / C = 1000-5000的苯乙酮与含有明确定义的手性Rh络合物CpRhCl [（R，R）- tsdpen]。
• A practical synthesis of optically active aromatic epoxides via asymmetric transfer hydrogenation of α-chlorinated ketones with chiral rhodium–diamine catalyst
  作者：Takayuki Hamada、Takayoshi Torii、Kunisuke Izawa、Takao Ikariya

  DOI：10.1016/j.tet.2004.06.076

  日期：2004.8

  A practical method for the synthesis of optically active aromatic epoxides has been developed via the formation of optically active α-chlorinated alcohols and intramolecular etherification. Optically active alcohols with up to 99% ee can be obtained from the asymmetric reduction of aromatic ketones with a substrate/catalyst ratio of 1000–5000 using a formic acid/triethylamine mixture containing a well-defined

  通过形成光学活性的α-氯化醇和分子内醚化，已经开发了一种合成光学活性的芳族环氧化物的实用方法。使用含有明确定义的手性Rh络合物Cp * RhCl [（[R， [R）-Tsdpen]。由于二胺基Cp * Rh（III）氢化物配合物的配位饱和特性，用手性Rh催化剂不对称还原α-氯化芳族酮的特征是快速且羰基选择性转化。还原的结果受酮底物的结构以及氢源（如甲酸或2-丙醇）的影响很大。无需特殊纯化即可在该反应中使用市售的试剂和溶剂。一锅法或两锅法的这种环氧化物合成方法是实用的，对于从α-氯代酮大规模生产旋光性苯乙烯氧化物特别有用。
• ‘Green’ synthesis of important pharmaceutical building blocks: enzymatic access to enantiomerically pure α-chloroalcohols
  作者：Dunming Zhu、Chandrani Mukherjee、Ling Hua

  DOI：10.1016/j.tetasy.2005.08.037

  日期：2005.10

  α-chloroketones, the precursors of pharmaceutically valuable α-chloroalcohols. Several highly active and enantioselective ketoreductases were found and their applications to the synthesis of both enantiomers of these α-chloroalcohols were demonstrated on a preparative scale. This offers a convenient, ‘green’ access to this type of important pharmaceutical building blocks.

  筛选了三十一种重组酮还原酶，以减少六种α-氯酮（药学上有价值的α-氯醇的前体）的还原。发现了几种高活性和对映选择性的酮还原酶，并以制备规模证明了它们在合成这些α-氯醇的两种对映异构体中的应用。这为此类重要的药物构建基块提供了便捷的“绿色”通道。
• Gene Cloning and Expression of<i>Leifsonia</i>Alcohol Dehydrogenase (LSADH) Involved in Asymmetric Hydrogen-Transfer Bioreduction to Produce (<i>R</i>)-Form Chiral Alcohols
  作者：Kousuke INOUE、Yoshihide MAKINO、Tohru DAIRI、Nobuya ITOH

  DOI：10.1271/bbb.70.418

  日期：2006.1

  The gene encoding Leifsonia alcohol dehydrogenase (LSADH), a useful biocatalyst for producing (R)-chiral alcohols, was cloned from the genomic DNA of Leifsonia sp. S749. The gene contained an opening reading frame consisting of 756 nucleotides corresponding to 251 amino acid residues. The subunit molecular weight was calculated to be 24,999, which was consistent with that determined by polyacrylamide gel electrophoresis. The enzyme was expressed in recombinant Escherichia coli cells and purified to homogeneity by three column chromatographies. The predicted amino acid sequence displayed 30–50% homology to known short chain alcohol dehydrogenase/reductases (SDRs); moreover, the NADH-binding site and the three catalytic residues in SDRs were conserved. The recombinant E. coli cells which overexpressed lsadh produced (R)-form chiral alcohols from ketones using 2-propanol as a hydrogen donor with the highest level of productivity ever reported and enantiomeric excess (e.e.).

  编码Leifsonia醇脱氢酶(LSADH)的基因是从Leifsonia sp. S749的基因组DNA中克隆得到的，这是一种生产(R)-手性醇的有用生物催化剂。该基因包含一个开放阅读框，由756个核苷酸组成，对应251个氨基酸残基。亚基分子量计算为24,999，与通过聚丙烯酰胺凝胶电泳确定的值一致。该酶在重组大肠杆菌细胞中表达，并通过三次柱层析纯化至同质。预测的氨基酸序列显示出与已知的短链醇脱氢酶/还原酶(SDRs)有30-50%的同源性；此外，NADH结合位点和SDRs中的三个催化残基被保留。过表达lsadh的重组大肠杆菌细胞使用2-丙醇作为供氢体，从酮生产(R)-形式的手性醇，生产效率达到迄今为止报道的最高水平，并且具有高度对映体过量(e.e.)。