(2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile | 36770-70-4

• 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: (2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile
• 英文别名: (S)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile；(4S)-(-)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropylbutanol；(S)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropylbutanol；2-(3,4-dimethoxyphenyl)-5-hydroxy-2-propan-2-ylpentanenitrile
• CAS: 36770-70-4
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: XCVXXCRTGFYXRO-UHFFFAOYSA-N

物化性质

• 沸点：
  430.1±45.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile 在 三苯基膦 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 生成 (-)-3-(3,4-二甲氧基苯基)-6-[(5,6-二甲氧基苯乙基)甲基氨基]己烷-3-甲腈
  参考文献：
  名称：

  (S)-和(R)-维拉帕米的酶介合成

  摘要：

  描述了脂肪酶介导的 (S)-和 (R)-维拉帕米合成。合成序列的关键步骤是由脂肪酶 PS 介导的烯丙醇 (Z)-(±)-2 的对映选择性乙酰化，得到乙酸衍生物 (Z,R)-(-)-3 (ee 92%)后者及其对映异构体 (Z,S)-(+)-3 (ee 92%) 的 Ireland-Claisen 重排得到酸衍生物 (E,R)-(-)-4 (ee 94%) 和(E,S)-(+)-4 (ee 93%)，分别是 (S)- 和 (R)-维拉帕米的前体。

  DOI：

  10.1002/1099-0690(200104)2001:7<1349::aid-ejoc1349>3.0.co;2-9
• 作为产物：
  描述：

  3-甲基-2-(3,4-二甲氧基苯基)丁腈 在 盐酸 、 甲醇 、 氢氧化钾 、 pseudomonas fluorescens lipase 、 sodium hydride 作用下， 以 正己烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile
  参考文献：
  名称：

  Enzyme-catalysed improved resolution of (RS)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol

  摘要：

  Resolutions of (RS)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol 1 using various enzymes were performed. Among them, Pseudomonas fluorescens resolved it with moderate stereoselectivity (E=13) and reacted faster with the (S)-enantiomer. To optimize enzyme-catalysed reaction conditions for the resolution, the effect of solvents and additives was studied. In n-hexane:ethyl acetate (9:1), both reaction rate and selectivity were high. When pyridine, potassium carbonate and molecular sieves were used as additives, the enantiomeric excess of the (R)-enantiomer was 99, 99 and 98% at 52-60% conversion, respectively. However, in diisopropyl ether, the enantiomeric excess of unreacted alcohol (R)-1 was up to 99% at 70% conversion without additives. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00389-4

文献信息

• Design, Synthesis, and Preliminary Pharmacological Evaluation of 4-Aminopiperidine Derivatives as N-Type Calcium Channel Blockers Active on Pain and Neuropathic Pain
  作者：Elisabetta Teodori、Elisabetta Baldi、Silvia Dei、Fulvio Gualtieri、Maria Novella Romanelli、Serena Scapecchi、Cristina Bellucci、Carla Ghelardini、Rosanna Matucci

  DOI：10.1021/jm049923l

  日期：2004.11.1

  Several compounds with a 4-aminopiperidine scaffold decorated on both nitrogen atoms by alkyl or acyl moieties containing the structural motifs of verapamil and of flunarizine, as well as those that are more frequent in known N-type calcium channel antagonists, have been synthesized. Antinociceptive activity on the mouse hot-plate test was used to select molecules to be submitted to further studies

  已经合成了几种具有4-氨基哌啶骨架的化合物，它们在两个氮原子上都被包含维拉帕米和氟那利嗪的结构基序的烷基或酰基部分修饰，以及在已知的N型钙通道拮抗剂中更常见的那些。使用小鼠热板试验的抗伤害感受活性来选择要进一步研究的分子。在PC12大鼠嗜铬细胞瘤克隆细胞系上对活性化合物进行了体外测试，以评估其对N型钙通道和神经性疼痛大鼠模型的作用。已选择了两种具有N型钙通道拮抗作用且对疼痛和神经性疼痛具有有效作用的化合物（3和18）进行进一步研究。
• Synthesis of the Verapamil Intermediate through the Quaternary Carbon-Constructing Allylic Substitution
  作者：Yuichi Kobayashi、Ryohei Saeki、Yutaro Nanba、Yuta Suganuma、Masao Morita、Keita Nishimura

  DOI：10.1055/s-0036-1588518

  日期：2017.12

  present study, the key secondary allylic picolinate was synthesized via Pd(PPh3)4-catalyzed coupling of the TBS ether of (R,Z)-4-iodo-5-methylhex-3-en-2-ol with allyl-MgBr. Allylic substitution of the picolinate with the copper reagent derived from 3,4-(MeO)2C6H3MgBr and Cu(acac)2 in a 2:1 ratio afforded the anti SN2′ product with complete chirality transfer and 91% regioselectivity. Synthetic manipulation

  在本研究中，关键的仲烯丙基吡啶甲酸酯是通过 Pd(PPh3)4 催化的 (R,Z)-4-iodo-5-methylhex-3-en-2-ol 的 TBS 醚与烯丙基-溴化镁。吡啶甲酸酯与源自 3,4-(MeO)2C6H3MgBr 和 Cu(acac)2 的铜试剂以 2:1 的比例进行烯丙基取代，得到了具有完全手性转移和 91% 区域选择性的抗 SN2' 产物。烯烃部分的合成操作导致产生腈基，从而产生用于合成 (S)-维拉帕米的中间体。
• De Novo Synthesis of Conjugates
  申请人：Riggs-Sauthier Jennifer

  公开号：US20100184989A1

  公开（公告）日：2010-07-22

  The invention provides methods for the preparation of small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer obtained from a water-soluble oligomer composition. Such drugs are produced through modification of a synthetic pathway to attach the oligomer to an intermediate compound followed by completion of the synthetic path.

  本发明提供了一种制备化学修饰的小分子药物的方法，其中化学修饰是通过共价连接来自水溶性寡聚物组合物的水溶性寡聚物进行的。这种药物是通过修改合成途径将寡聚物连接到中间化合物，然后完成合成途径而生产的。
• Oligomer-Calcium Channel Blocker Conjugates
  申请人：Ren Zhongxu

  公开号：US20110098273A1

  公开（公告）日：2011-04-28

  The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water soluble oligomer.

  本发明提供了通过共价连接水溶性寡聚体对小分子药物进行化学修饰的药物。本发明的结合物在经过多种给药途径的给药后，表现出与未连接水溶性寡聚体的小分子药物不同的特性。
• OLIGOMER-CALCIUM CHANNEL BLOCKER CONJUGATES
  申请人：NEKTAR THERAPEUTICS

  公开号：US20140323529A1

  公开（公告）日：2014-10-30

  The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water soluble oligomer.

  该发明提供了通过共价连接水溶性寡聚体对化学修饰的小分子药物。该发明的共轭物在通过任何一种给药途径进行给药时，表现出与未连接水溶性寡聚体的小分子药物不同的特性。