2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile | 158705-89-6

• 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: 2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile
• 英文别名: (R)-2-hydroxy-2-(3,4-dimethoxyphenyl)acetonitrile；(R)-2-hydroxy-2-(3,4-dimethoxy)acetonitrile；(R)-(+)-2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile；Veratraldehyde cyanohydrin；(2R)-2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile
• CAS: 158705-89-6
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: SFIAWXDEIAXFOS-QMMMGPOBSA-N

物化性质

• 沸点：
  356.8±42.0 °C(predicted)
• 密度：
  1.193±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile 在 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 五氯化磷 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (1R,3S,4R)-(+)-6,7-dimethoxy-4-hydroxy-1-methyl-3-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  A simple enzymatic synthesis of (3S,4R)-(+)-4-hydroxy-3-phenyltetrahydroisoquinolines

  摘要：

  An efficient versatile method is presented for the stereospecific synthesis of (+)-4hydroxy-3-phenyltetrahydroisoquinoline 11 and 12 using (R)-arylcyanohydrins as the chiral starting material. From this asymmetric core, the synthetic process proceeds with development of the S absolute stereochemistry for the phenyl group at C-3 and the R configuration at C-1 of the target heterocycle. As the protective group protocol allows the stereospecific deprotection at C4, (3S,4R)-(+)-4-hydroxy-3-phenyltetrahydroisoquinolines have been prepared using this process.

  DOI：

  10.1016/0957-4166(94)80127-4
• 作为产物：
  描述：

  藜芦醛氰醇 生成 2-(3,4-dimethoxyphenyl)-2-hydroxyacetonitrile
  参考文献：
  名称：

  A simple enzymatic synthesis of (3S,4R)-(+)-4-hydroxy-3-phenyltetrahydroisoquinolines

  摘要：

  An efficient versatile method is presented for the stereospecific synthesis of (+)-4hydroxy-3-phenyltetrahydroisoquinoline 11 and 12 using (R)-arylcyanohydrins as the chiral starting material. From this asymmetric core, the synthetic process proceeds with development of the S absolute stereochemistry for the phenyl group at C-3 and the R configuration at C-1 of the target heterocycle. As the protective group protocol allows the stereospecific deprotection at C4, (3S,4R)-(+)-4-hydroxy-3-phenyltetrahydroisoquinolines have been prepared using this process.

  DOI：

  10.1016/0957-4166(94)80127-4

文献信息

• A High‐Throughput Screening Method for the Directed Evolution of Hydroxynitrile Lyase towards Cyanohydrin Synthesis
  作者：Yu‐Cong Zheng、Liang‐Yi Ding、Qiao Jia、Zuming Lin、Ran Hong、Hui‐Lei Yu、Jian‐He Xu

  DOI：10.1002/cbic.202000658

  日期：2021.3.16

  Hydroxynitrile lyases (HNLs) catalyze the enantioselective cleavage/formation of cyanohydrins. However, current methods for determining hydrocyanation are not suitable for mass screening of mutants for protein engineering of these biocatalysts. We demonstrate herein a chromogenic high‐throughput screening method for cyanohydrin synthesis that is validated by either substrate profiling or the directed evolution

  使生物氢氰化可测量：羟腈裂解酶 (HNL) 催化对映选择性裂解/形成氰醇。然而，目前确定氢氰化的方法不适合对这些生物催化剂的蛋白质工程进行突变体的大规模筛选。我们在此展示了一种用于氰醇合成的显色高通量筛选方法，该方法通过底物分析或 HNL 的定向进化进行验证。
• A new (R)-hydroxynitrile lyase from Prunus mume: asymmetric synthesis of cyanohydrins
  作者：Samik Nanda、Yasuo Kato、Yasuhisa Asano

  DOI：10.1016/j.tet.2005.08.105

  日期：2005.11

  A new hydroxynitrile lyase (HNL) was isolated from the seed of Japanese apricot (Prunus mume). The enzyme has similar properties with HNL isolated from other Prunus species and is FAD containing enzyme. It accepts a large number of unnatural substrates (benzaldehyde and its variant) for the addition of HCN to produce the corresponding cyanohydrins in excellent optical and chemical yields. A new HPLC

  从日本杏（Prunus mume）的种子中分离出一种新的羟腈裂解酶（HNL ）。该酶与从其他李属物种中分离的HNL具有相似的特性，并且是含FAD的酶。它接受大量非天然底物（苯甲醛及其变体）以添加HCN，从而以优异的光学和化学收率生产相应的氰醇。针对该酶开发了一种新的基于HPLC的对映选择性测定技术，该技术可促进在缓冲溶液（pH = 4.5）中将KCN添加到苯甲醛中。
• (R)- and (S)-cyanohydrins using oxynitrilases in whole cells
  作者：Eero Kiljunen、Liisa T Kanerva

  DOI：10.1016/0957-4166(96)00116-4

  日期：1996.4

  Almond meal and Sorghum bicolor shoots were used as the sources of oxynitrilases for the preparation of a number (R)- and (S)-arylcyanohydrins, respectively, from the corresponding aldehydes in diisopropyl ether. Two different in situ methods were used to introduce hydrogen cyanide into the reaction mixture. In method 1, acetone cyanohydrin decomposes enzymatically and/or chemically to hydrogen cyanide

  杏仁粉和高粱双色芽被用作氧硝化酶的来源，分别从二异丙基醚中的相应醛中制备许多（R）-和（S）-芳基氰醇。使用两种不同的原位方法将氰化氢引入反应混合物中。在方法1中，丙酮氰醇通过酶和/或化学方式分解为氰化氢。在方法2中，氰化氢从二异丙醚中的溶液从反应容器的一个腔室中自由蒸发，最终到达另一个溶解在反应混合物中的区域。
• Structure-Guided Tuning of a Hydroxynitrile Lyase to Accept Rigid Pharmaco Aldehydes
  作者：Yu-Cong Zheng、Fu-Long Li、Zuming Lin、Guo-Qiang Lin、Ran Hong、Hui-Lei Yu、Jian-He Xu

  DOI：10.1021/acscatal.0c01103

  日期：2020.5.15

  benzo-ketal aldehyde which was proved to be resistant against racemization during the deprotection step, with dramatically improved productivity (>95% conversion vs <1%). X-ray structure analysis and kinetic study revealed the side chain of L331 tunes the substrate adaptability of bulky and rigid benzo-ketal aldehyde, thereby facilitating the formation of a series of valuable unnatural cyanohydrins in high

  由酶促氢氰化作用产生的手性邻位C–O / C–N双官能团代表了一种有用的方法。然而，β的药效建设2用这种方法肾上腺素受体激动剂残留的缩醛基脱保护过程中，因为苯甲醇的完全外消旋化的一个巨大的挑战。在这项研究中，对来自李属李（Pc）的羟腈裂解酶进行结构指导的重新设计HNL5）可使硬质苯并缩酮醛发生高度对映选择性的氢氰化反应，事实证明该脱苯酮反应过程中的苯并酮缩醛具有抗外消旋作用，生产率大大提高（转化率> 95％，<1％）。X射线结构分析和动力学研究表明，L331的侧链可调节大体积和刚性苯并缩酮醛的底物适应性，从而有助于以高对映体纯度和高收率形成一系列有价值的非天然氰醇。此外，变体HNL L331A被成功地应用于（的克级化学-酶促合成- [R）-salmeterol，长期β 2肾上腺素受体激动剂，其光学纯形式（> 99％ee）的与总产率54％，是报告的最高值。
• Novel (R)-oxynitrilase sources for the synthesis of (R)-cyanohydrins in diisopropyl ether
  作者：Eero Kiljunen、Liisa T. Kanerva

  DOI：10.1016/s0957-4166(97)00080-3

  日期：1997.4

  Apple, apricot, cherry and plum meal were prepared from the seeds or kernels of mature garden fruits. The preparations as well as almond meal were used as the source of (R)-oxynitrilase for the synthesis of aliphatic and aromatic cyanohydrins in diisopropyl ether in the presence of 0.1 M tartrate buffer [2% (v/v), pH 5.4]. Apple meal as the most favourable of the enzyme preparations accepts also sterically hindered aldehydes (e.g., pivalaldehyde) as substrates, leading to (R)-cyanohydrins with high enantiopurity (usually ee>90%). (C) 1997 Elsevier Science Ltd.