(R)-(-)-1-cyano-1-(3,4-methylenedioxyphenyl)methyl acetate | 119904-37-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (R)-(-)-1-cyano-1-(3,4-methylenedioxyphenyl)methyl acetate
• 英文别名: [(R)-1,3-benzodioxol-5-yl(cyano)methyl] acetate
• CAS: 119904-37-9
• 化学式: C₁₁H₉NO₄
• 分子量: 219.197
• InChiKey: QLJQZNQAUINIDB-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-(-)-1-cyano-1-(3,4-methylenedioxyphenyl)methyl acetate 在 lithium aluminium tetrahydride 作用下， 生成 (1R)-2-amino-1-(1,3-dioxaindan-5-yl)ethan-1-ol
  参考文献：
  名称：

  Microbial hydrolysis of substituted mandelonitrile acetates and its application to the synthesis of optically active physiological ethanolamines.

  摘要：

  DOI：

  10.1271/bbb1961.53.281
• 作为产物：
  描述：

  α-acetoxy-2-(3,4-methylenedioxyphenyl)acetonitrile 生成 (R)-(-)-1-cyano-1-(3,4-methylenedioxyphenyl)methyl acetate
  参考文献：
  名称：

  Combination of the lipase-catalysed resolution with the Mitsunobu esterification in one pot

  摘要：

  A chemo-enzymatic method for the preparation of homochiral esters of 14 secondary alcohols with 100% theoretical yields is described in one pot through two steps: the lipase-catalysed kinetic resolution followed by the Mitsunobu esterification of the free alcohol enantiomer in situ in the resolution mixture. Mathematical equations which link the enzymatic and chemical steps were derived, resulting in an enantioconvergent synthetic tool for the preparation of chiral intermediates.

  DOI：

  10.1016/0957-4166(95)00224-d

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。
• Lipase-catalyzed kinetic resolution with in situ racemization: one-pot synthesis of optically active cyanohydrin acetates from aldehydes
  作者：Minoru Inagaki、Jun Hiratake、Takaaki Nishioka、Junichi Oda

  DOI：10.1021/ja00024a047

  日期：1991.11

  amounts of timolol with optimal base-line separation were 18.9 and 19.9 pg/g of dry CSP, respectively (Figure 2), and in connection with the aforementioned polarimetric study of propranolol, with fair resolution but no base-line separation, 400 p g / g of dry CSP], work aimed at increasing the capacity of analogous imprinted polymers is in progress and will further increase the applicability of the technique

  随意。尽管此处显示的容量与例如使用蛋白质纤维素酶的生物替代方法相比非常好 [具有最佳基线分离的噻吗洛尔的量分别为 18.9 和 19.9 pg/g 干 CSP（图 2），与上述普萘洛尔的极化研究有关，具有良好的分辨率但没有基线分离，400 pg / g 的干 CSP]，旨在提高类似印迹聚合物容量的工作正在进行中，并将进一步提高其适用性用于（半）制备性分离化合物（如 &blockers）的纯对映异构体的技术。然而，我们认为今天已经可以使用所描述的技术在技术规模上去除污染的少量不想要的对映异构体。
• One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Quinidine-Catalyzed Transhydrocyanation Coupled with Lipase-Catalyzed Kinetic Resolution in Organic Solvent
  作者：Minoru Inagaki、Akihiko Hatanaka、Mitsuo Mimura、Jun Hiratake、Takaaki Nishioka、Jun’ichi Oda

  DOI：10.1246/bcsj.65.111

  日期：1992.1

  transhydrocyanation allows for in situ racemization of the unreacted cyanohydrins and concurrent kinetic resolution by lipase enabled the preparation of (S)-3b–d with 40–82% e.e. in more than 50% yield. Polymer-supported cinchona alkaloid was also used as a catalyst for this one-pot reaction and showed the comparable chemical and optical yield to that for the soluble monomeric alkaloid. The insoluble polymer and lipase

  开发了一种新的一锅合成方法来制备旋光氰醇乙酸酯。通过奎尼丁催化的氢氰化反应从醛和丙酮氰醇中生成外消旋氰醇，然后使用乙酸异丙烯酯作为酰化剂，通过脂肪酶以立体选择性方式将所得氰醇 2a-j 乙酰化。多种醛 1a-j 成功地转化为相应的氰醇乙酸酯 3a-j，其 ee 为 47-95%，而没有分离不稳定的氰醇 2。此外，碱催化转移氢氰化的可逆性质允许未反应的氰醇原位外消旋化脂肪酶同时进行动力学拆分使 (S)-3b-d 能够以 50% 以上的产率制备 40-82% ee 的 (S)-3b-d。聚合物负载的金鸡纳生物碱也被用作这种一锅反应的催化剂，并显示出与可溶性单体生物碱相当的化学和光学产率。不溶性聚合物和脂肪酶...
• 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。
• Enzymatic preparation of optically active cyanohydrin acetates
  作者：Andreas van Almsick、Joachim Buddrus、Petra Hönicke-Schmidt、Kurt Laumen、Manfred P. Schneider

  DOI：10.1039/c39890001391

  日期：——

  A series of cyanohydrin acetates (1)–(47) of widely varying structures, potential chiral building blocks for numerous synthetic applications, has been prepared in good chemical and often high optical yields by enzymatic hydrolysis of their racemic acetates in the presence of an ester hydrolase from Pseudomonas sp.

  通过在酯存在下进行酶促外消旋乙酸酯的酶水解，可以制备出具有良好化学性质且通常具有高光学收率的一系列结构广泛变化的氰氨醇乙酸酯（1）–（47），可用于许多合成应用假单胞菌（Pseudomonas sp）的水解酶。