isopropyl (R)-4-chloro-3-hydroxybutanoic acid ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: isopropyl (R)-4-chloro-3-hydroxybutanoic acid ester
• 英文别名: (R)-isopropyl 4-chloro-3-hydroxybutanoate；(R)-(+)-4-chloro-3-hydroxybutyric acid isopropyl ester；propan-2-yl (3R)-4-chloro-3-hydroxybutanoate
• 化学式: C₇H₁₃ClO₃
• 分子量: 180.631
• InChiKey: BZXNYWHUGJDAFS-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  isopropyl (R)-4-chloro-3-hydroxybutanoic acid ester 在 吡啶 、 sodium azide 、 氢气 、 铑 作用下， 以 甲醇 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 18.5h， 生成
  参考文献：
  名称：

  (R)-4-羟基-2-氧代-1-吡咯烷乙酰胺的制备 方法

  摘要：

  一种(R)‑4‑羟基‑2‑氧代‑1‑吡咯烷乙酰胺的制备方法，包括如下步骤：(1)以R‑4‑氯‑3‑羟基丁酸酯为起始原料，与叠氮化试剂进行叠氮化反应，得到中间体I；(2)将中间体I进行还原反应，获得中间体II；(2)将中间体II与卤代乙酸酯进行缩合反应，获得中间体Ⅲ；(3)将中间体Ⅲ进行关环反应得到中间体IV；(4)将中间体IV进行氨解反应，得到目标产物(R)‑4‑羟基‑2‑氧代‑1‑吡咯烷乙酰胺。本发明至少可获得38%以上较理想收率的(R)‑4‑羟基‑2‑氧代‑1‑吡咯烷乙酰胺产物，开辟了一条新的(R)‑4‑羟基‑2‑氧代‑1‑吡咯烷乙酰胺合成路线。

  公开号：

  CN105330582B
• 作为产物：
  描述：

  i-propyl 4-chloro-3-hydroxybutyrate 生成 isopropyl (R)-4-chloro-3-hydroxybutanoic acid ester
  参考文献：
  名称：

  A novel generation of optically active ethyl 4-chloro-3-hydroxybutyrate as a C4 chiral building unit using microbial dechlorination

  摘要：

  A novel procedure for the generation of optically active ethyl 4-chloro-3-hydroxybutyrate using bacterial cells was developed. Ethyl (S)-4-chloro-3-hydroxybutyrate was prepared by Pseudomonas sp. OS-K-29, which stereoselectively assimilates 2,3-dichloro-1-propanol. The reaction was based on its kinetic dehalogenation for both enantiomers using the resting cells. The obtained 4-chloro-3-hydroxybutyrate rate had high enantiomeric excess of >98%, with a yield of 33% at the microbial resolution step. Moreover, several C4 compounds having the 4-chloro-3-hydroxyl function were also resolved and gave good enantiomeric purities (>95 %ee). Ethyl (R)-4-chloro-3-hydroxybutyrate was also obtained with high enantiomeric purity (>98 %ee) using the cells of Pseudomonas sp DS-K-NR818. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00410-7

文献信息

• Biocatalytic deuterium- and hydrogen-transfer using over-expressed ADH-‘A’: enhanced stereoselectivity and²H-labeled chiral alcohols
  作者：Klaus Edegger、Christian C. Gruber、Tina M. Poessl、Sabine R. Wallner、Iván Lavandera、Kurt Faber、Frank Niehaus、Juergen Eck、Reinhold Oehrlein、Andreas Hafner、Wolfgang Kroutil

  DOI：10.1039/b602487d

  日期：——

  Employing the over-expressed highly organic solvent tolerant alcohol dehydrogenase ADH-‘A’ from Rhodococcus ruber DSM 44541, versatile building blocks, which were not accessible by the wild type catalyst, were obtained in > 99% e.e.; furthermore, employing d8-2-propanol as deuterium source, stereoselective biocatalytic deuterium transfer was made feasible to furnish enantiopure deuterium labeled sec-alcohols on a preparative scale employing a single enzyme.

  利用来自红球菌DSM 44541的高度有机溶剂耐受性乙醇脱氢酶ADH-“A”进行过量表达，获得了通过野生型催化剂无法获得的多种高效构件，其对映体纯度超过99%；此外，采用d8-2-丙醇作为氘源，实现了利用单一酶在制备规模上进行立体选择性生物催化氘转移，从而制备了手性纯氘标记的二级醇。
• Enzymatic Reduction of Ketones in “Micro-aqueous” Media Catalyzed by ADH-A from <i>Rhodococcus </i><i>ruber</i>
  作者：Gonzalo de Gonzalo、Iván Lavandera、Kurt Faber、Wolfgang Kroutil

  DOI：10.1021/ol070679c

  日期：2007.5.1

  micro-aqueous organic systems (99% v v-1) were successfully employed for the biocatalytic reduction of ketones catalyzed by alcohol dehydrogenase ADH-A from Rhodococcus ruber via hydrogen transfer. A clear correlation between the log P of the organic solvent and the enzyme activity--the higher, the better--was found. The use of organic solvents allowed highly stereoselective enzymatic carbonyl reductions at substrate

  单相和双相水性有机溶剂系统（50％v v-1）以及微水有机系统（99％v v-1）已成功用于乙醇脱氢酶ADH-A催化从乙醇中还原酮的生物催化还原。红球菌通过氢转移。发现有机溶剂的log P与酶活性之间存在明显的相关性-越高越好。使用有机溶剂可在接近2.0 M的底物浓度下实现高度立体选择性的酶羰基还原反应。
• Asymmetric anti-Prelog reduction of ketones catalysed by Paracoccus pantotrophus and Comamonas sp. cells via hydrogen transfer
  作者：Iván Lavandera、Brigitte Höller、Alexander Kern、Ursula Ellmer、Anton Glieder、Stefaan de Wildeman、Wolfgang Kroutil

  DOI：10.1016/j.tetasy.2008.08.005

  日期：2008.8

  A broad range of ketones including methyl-aryl-, methyl-alkyl-, cyclic and sterically hindered ketones were reduced to the corresponding anti-Prelog alcohols with moderate to excellent stereoselectivities by employing lyophilised cells of Paracoccus pantotrophus DSM 11072 and Comamonas sp. DSM 15091 via hydrogen transfer. The reduction equivalents were provided using 2-propanol as a hydride donor.

  使用泛酸副球菌DSM 11072和Comamonas sp。的冻干细胞，将包括甲基-芳基-，甲基-烷基-，环状和空间位阻的酮在内的多种酮还原为相应的具有适度至优异立体选择性的抗Prelog醇。DSM 15091通过氢转移。使用2-丙醇作为氢化物供体提供还原当量。例如，苯乙酮被还原为相应的（R）-对映体，其ee> 99％。
• Chemoenzymatic Dynamic Kinetic Resolution of β-Halo Alcohols. An Efficient Route to Chiral Epoxides
  作者：Oscar Pàmies、Jan-E. Bäckvall

  DOI：10.1021/jo026157m

  日期：2002.12.1

  Enzymatic resolution of beta-chloro alcohols in combination with ruthenium-catalyzed alcohol isomerization led to a successful dynamic kinetic resolution (conversion up to 99% and ee up to 97%). The efficiency of the DKR is dramatically reduced when beta-bromo alcohols are used. The presence of the bromo substituent causes decomposition of the ruthenium catalysts, which triggers the progressive deactivation

  β-氯醇的酶促拆分与钌催化的醇异构化相结合，成功实现了动态动力学拆分（转化率高达99％，ee高达97％）。当使用β-溴醇时，DKR的效率会大大降低。溴取代基的存在会导致钌催化剂分解，从而触发酶的逐步失活。该方法的合成效用已通过不同手性环氧化物的实际合成得到说明。
• Non-Racemic Halohydrinsvia Biocatalytic Hydrogen-Transfer Reduction of Halo-Ketones and One-Pot Cascade Reaction to Enantiopure Epoxides
  作者：Tina M. Poessl、Birgit Kosjek、Ursula Ellmer、Christian C. Gruber、Klaus Edegger、Kurt Faber、Petra Hildebrandt、Uwe T. Bornscheuer、Wolfgang Kroutil

  DOI：10.1002/adsc.200505094

  日期：2005.11

  possibility for a follow-up reaction of halohydrins is the ring closure to the corresponding epoxide. A novel “one pot-one step strategy” was employed to obtain the enantiopure epoxide from the α-chloro-ketone in a cascade like fashion at pH>12 involving biocatalytic hydrogen transfer reduction and in situ chemo-catalyzed ring closure.

  通过使用红球菌作为冻干细胞催化剂或得自荧光假单胞菌DSM 50106（PF-ADH）的醇脱氢酶制剂，α-氯酮的生物催化氢转移还原可提供非外消旋的氯醇。对于所研究的所有底物，红球菌均严格提供“ Prelog”产品，而PF-ADH显示出分散的立体偏好。卤代醇的后续反应的一种可能性是与相应的环氧化物的闭环。一种新颖的“一站式一步策略”被用于从α-氯代酮中以级联方式在pH> 12的条件下获得对映纯的环氧化物，包括生物催化的氢转移还原和原位化学催化的闭环反应。