(R)-2-hydroxy-2-(3,4-methylenedioxyphenyl)acetonitrile | 10017-05-7

• 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)-2-hydroxy-2-(3,4-methylenedioxyphenyl)acetonitrile
• 英文别名: (R)-1,3-Benzodioxole-5-acetonitrile；(2R)-2-(1,3-benzodioxol-5-yl)-2-hydroxyacetonitrile
• CAS: 10017-05-7
• 化学式: C₉H₇NO₃
• 分子量: 177.159
• InChiKey: JWZKLCWLXKKOLL-ZETCQYMHSA-N

物化性质

• 沸点：
  366.0±42.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  (R)-2-hydroxy-2-(3,4-methylenedioxyphenyl)acetonitrile 在 吡啶 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 5.5h， 生成 (4S,5R)-5-Benzo[1,3]dioxol-5-yl-3-cyclopropyl-4-methyl-oxazolidin-2-one
  参考文献：
  名称：

  Stereoselective Synthesis of (S)-3,4-Methylenedioxyamphetamines from (R)-Cyanohydrins

  摘要：

  AbstractA stereoselective synthesis of (S)‐3,4‐methylenedioxyamphetamines (S)‐7, which are highly interesting as psychoactive compounds, is described. Starting from readily available (R)‐cyanohydrins (R)‐2 the 2‐amino‐1‐aryl alcohols (1R,2S)‐4 were obtained with high diastereoselectivity by addition of Grignard reagents to the O‐protected cyanohydrins (R)‐3, transimination of the addition products A with primary amines, and hydrogenation of the imino intermediates B with NaBH4. For the hydrogenation of the benzylic hydroxyl group in the 1,2‐amino alcohols (1R,2S)‐4 a new, very efficient method was developed. The optically pure amphetamines (S)‐7 were obtained under very mild conditions by catalytic hydrogenation of the oxazolidinones (4S,5R)‐6, which were readily available by phosgenation of the amino alcohols (1R,2S)‐4.

  DOI：

  10.1002/chem.19970030825
• 作为产物：
  描述：

  胡椒醛 以50%的产率得到
  参考文献：
  名称：

  BRUSSEE, J.;LOOS, W. T.;KRUSE, C. G.;VAN, DER GEN A., TETRAHEDRON, 46,(1990) N, C. 979-986

  摘要：

  DOI：

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。
• Enantioselective addition of trimethylsilyl cyanide to aldehydes catalysed by bifunctional BINOLAM-AlCl versus monofunctional BINOL-AlCl complexes
  作者：Jesús Casas、Carmen Nájera、José M. Sansano、José M. Saá

  DOI：10.1016/j.tet.2004.06.137

  日期：2004.11

  applied to the Shibasaki synthesis of epothilone A. All the evidence available for the BINOLAM-AlCl enantioselective addition of TMSCN to aldehydes call for the intervention of a hydrocyanation reaction, addition of a catalytic amount of hydrogen cyanide, generated in situ, to an aldehyde, followed by O-silylation. In order to determine the role of the basic amino groups of BINOLAM, comparative studies

  醛的高度对映选择性氰化是通过使用衍生自3,3'-双（二乙基氨基甲基）取代的联萘酚（BINOLAM）和氯化二甲基铝的双官能催化剂进行的。该添加物的范围很广，并且在甲苯中，在4ÅMS和三苯基氧化膦作为添加剂的情况下，在-20至-40°C的温度下效果最佳。的（[R ）-或（小号使用（当）-cyanohydrins结果小号或（ - ）- [R）-BINOLAM-AlCl配合物。有价值的配体可以通过简单的提取后处理进行回收，并在不损失效率的情况下进行回收（无论是化学产率还是立体化学产率）。该方法学适用于Shibasaki合成埃坡霉素A的过程。所有可将BINOLAM-AlCl TMSCN对醛选择性加成到醛中的证据都要求进行氢氰化反应，即在原位生成催化量的氰化氢。醛，然后进行O-甲硅烷基化。为了确定BINOLAM的碱性氨基的作用，对单官能的1,1'-联萘酚衍生的复合物BINOL-AlCl进行了比较研究。
• Stereoselective synthesis of (1R)- and (1R,2S)-1-aryl-2-alkylamino alcohols from (R)-cyanohydrins
  作者：Franz Effenberger、Beate Gutterer、Jürgen Jäger

  DOI：10.1016/s0957-4166(96)00527-7

  日期：1997.2

  Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without racemization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alcohols (1R,2S)-4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 and (1R,2S)-9 can be prepared either by reductive alkylation

  在不消旋的情况下，用LiAlH 4氢化（R）-氰醇（R）-1 ，得到（R）-2-氨基醇（R）-3 。（1 - [R，2小号）-2-氨基醇（1R，2S）-4通过加入甲基格氏至O-甲硅烷基保护的氰醇（R）-2-具有高非对映选择性得到和用NaBH随后氢化4。N-烷基化的2-氨基醇（R）-8和（1R，2S）-9可以通过相应的2-氨基醇（R）-3和（1R，2S）-4的还原烷基化来制备，或通过格氏试剂加成产物与伯胺的转氨反应，然后再用NaBH 4氢化。与N-未取代的亚胺相比，在N-烷基亚氨基化合物的情况下，氢化的非对映选择性较低。
• 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。
• Preparation and Reactions of Certain Racemic and Optically Active Cyanohydrins Derived from 2-Chlorobenzaldehyde, 4-Fluorobenzaldehyde, Benzo[d][1,3]-dioxole-5-carbaldehyde and 2,3-Dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. Antimicrobial and in vitro Antitumor Evaluation of the Products
  作者：Yosef, Hisham Abdallah A.、Elmasry、Ibrahim, Nabila M.、Ismael, Eman H. I.、Mahran

  DOI：10.21608/ejchem.2017.3262

  日期：2017.4.30

  THE CHEMOENZYMATIC reaction of selected aldehydes, ……...namely 2-chlorobenzaldehyde (1a), 4-fluorobenzaldehyde (1b), benzo[d][1,3]dioxole-5-carbaldehyde (1c) and/or 2,3-dihydrobenzo [b] [1,4] dioxine-6-carbaldehyde (1d) with hydrogen cyanide in presence of (R)-oxynitrilase (R)-Pa HNL [EC 4.1.2.10] from almonds, as a chiral catalyst, gave the optically active cyanohydrin enantiomers (R)-2a-c, respectively.  Acetone cyanohydrin (3), was also used, as a transcyanating agent, to give the same products.  The racemic cyanohydrins (R,S)-2a-d have been synthesized, as well, by treating compounds 1a-d with aqueous potassium cyanide solution in presence of a saturated solution of sodium metabisulphite (Na2S2O5).  The optical purity of cyanohydrins (R)-2a-c was determined through their derivatization with (S)-naproxen chloride (S)-5 to the respective diastereomers (R,2S)-6a-c which were obtained in diastereomeric excess (de) values up to 93 % (1H NMR).  Heating compounds (R)-2a,b and / or their racemic analogues (R,S)-2a-c with concentrated hydrochloric acid gave the respective α-hydroxycarboxylic acids 7a-c.  Moreover, reduction of cyanohydrins (R,S)-2b,c under different conditions resulted in a hydrodecyanation giving the respective  primary alcohols 8a,b. Structures and configurations of the new compounds were confirmed with compatible elementary microanalyses and spectroscopic ( IR, 1H NMR, 13C NMR, MS and single crystal X-ray crystallography) measurements.  The antimicrobial activity of derivatives 6a-d against four bacterial species (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and two fungi (Aspergillus flavus and Candida albicans) were undertaken.  Moreover, compounds (R,2S)-6b, (R,2S)(S,2S)-6b and (R,2S)−6c were screened for their in virto antitumor activity against three human solid cancer cell lines (HCT 116, HepG2 and MCF-7).  In general, the tested compounds were found inactive or showed weak activities in comparison with the standard drugs.

  选定的醛类化合物，即2-氯苯甲醛（1a）、4-氟苯甲醛（1b）、苯并[d][1,3]二氧杂环戊烯-5-甲醛（1c）和/或2,3-二氢苯并[b][1,4]二氧杂环己烯-6-甲醛（1d），在氢氰酸与杏仁来源的(R)-氧腈酶（(R)-Pa HNL [EC 4.1.2.10]）作为手性催化剂的存在下，发生了化学酶促反应，分别得到了光学活性的氰醇对映体（R）-2a-c。此外，丙酮氰醇（3）也被用作氰基转移剂，得到了相同的产品。通过将化合物1a-d与含有饱和焦亚硫酸钠（Na2S2O5）溶液的氰化钾水溶液反应，也合成了外消旋的氰醇（R,S）-2a-d。通过与（S）-萘普生氯（S）-5的衍生化反应，确定了氰醇（R）-2a-c的光学纯度，得到了其在非对映体过量（de）值高达93%的非对映体（R,2S）-6a-c（1H NMR）。将化合物（R）-2a,b及其外消旋类似物（R,S）-2a-c与浓盐酸加热，得到了相应的α-羟基羧酸7a-c。此外，在不同条件下还原氰醇（R,S）-2b,c，得到了进行氢解反应的相应一级醇8a,b。通过配合元素微分析和光谱（IR、1H NMR、13C NMR、MS和单晶X射线晶体学）测量，确认了新化合物的结构和构型。对衍生物6a-d进行了抗微生物活性测试，针对四种细菌（枯草芽孢杆菌、金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌）和两种真菌（黄曲霉和白色念珠菌）。此外，化合物（R,2S）-6b、（R,2S）（S,2S）-6b和（R,2S）-6c在体外进行了抗肿瘤活性筛选，针对三种人类实体癌细胞系（HCT 116、HepG2和MCF-7）。总的来说，与标准药物相比，测试的化合物被发现不活跃或显示出微弱的活性。