(4R,5R)-4-羟基-5-羟甲基四氢呋喃-2-酮 | 78184-72-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (4R,5R)-4-羟基-5-羟甲基四氢呋喃-2-酮
• 英文名称: N-tert-butoxycarbonyl-(R)-baclofen
• 英文别名: 3R-1-t-butoxycarbonylamino-3-(4-chlorophenyl)butanoic acid；Boc-(R)-baclofen；(R)-4-((tert-butoxycarbonyl)amino)-3-(4-chlorophenyl)butanoic acid；4-tert-butoxycarbonylamino-(3R)-(4-chlorophenyl)butanoic acid；(3R)-3-(4-chlorophenyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 78184-72-2
• 化学式: C₁₅H₂₀ClNO₄
• 分子量: 313.781
• InChiKey: CKEIMCIEKVQSSN-NSHDSACASA-N

物化性质

• 沸点：
  475.7±40.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,5R)-4-羟基-5-羟甲基四氢呋喃-2-酮 在 盐酸 作用下， 反应 3.0h， 以74%的产率得到R(+)-巴氯芬盐酸盐
  参考文献：
  名称：

  Synthesis of homochiral R-Baclofen from S-glutamic acid.

  摘要：

  A stereoselective synthesis of R-Baclofen is presented, starting from S-pyroglutamic acid derivative 3. The key steps are the 1,4-conjugate addition of Grignard cuprate (p-ClPh)2CuMgCl to 3 and Barton-Decarboxylation of 6e to 7e.

  DOI：

  10.1016/s0957-4166(00)82107-2
• 作为产物：
  描述：

  2S,3R-1-t-butoxycarbonyl-3-(4-chlorophenyl)-5-oxo-pyrrolidine-2-carboxylic acid 在 N-甲基吗啉 、 1-氧化-2-巯基吡啶 、 lithium hydroxide 、 叔丁基硫醇 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 (4R,5R)-4-羟基-5-羟甲基四氢呋喃-2-酮
  参考文献：
  名称：

  Synthesis of homochiral R-Baclofen from S-glutamic acid.

  摘要：

  A stereoselective synthesis of R-Baclofen is presented, starting from S-pyroglutamic acid derivative 3. The key steps are the 1,4-conjugate addition of Grignard cuprate (p-ClPh)2CuMgCl to 3 and Barton-Decarboxylation of 6e to 7e.

  DOI：

  10.1016/s0957-4166(00)82107-2

文献信息

• Stereospecific Synthesis of (R)- and (S)-Baclofen and (R)- and (S)-PCPGABA (4-Amino-2-(4-chlorophenyl)butyric Acid) via (R)- and (S)-3-(4-Chlorophenyl)pyrrolidines.
  作者：Shigeyuki YOSHIFUJI、Mamoru KANAME

  DOI：10.1248/cpb.43.1302

  日期：——

  (R)- and (S)-Baclofen and (R)- and (S)-PCPGABA [4-amino-2-(4-chlorophenyl)butyric acid] were stereospecifically synthesized via (R)- and (S)-3-(4-chlorophenyl)pyrrolidines, starting from trans-4-hydroxy-L-proline. The syntheses involve two key operations, namely, 1) a stereoselective hydrogenation of dehydroproline derivatives controlled by the C-2 carboxyl function and 2) an effective ruthenium tetroxide oxidation to prepare chiral 3- and 4-(4-chlorophenyl)pyrrolidin-2-ones, which are dehydrated precursors of the target molecules.

  (R)-和(S)-巴克洛芬以及(R)-和(S)-PCPGABA [4-氨基-2-(4-氯苯基)丁酸] 是通过(R)-和(S)-3-(4-氯苯基)吡咯烷从反式-4-羟基-L-脯氨酸立体选择性合成的。合成过程包括两个关键操作，即：1) 由C-2羧基功能控制的脱氢脯氨酸衍生物的立体选择性氢化；2) 有效的四氧化铑氧化反应，以制备手性3-和4-(4-氯苯基)吡咯烷-2-酮，这些化合物是目标分子的脱水前体。
• Synthesis of β-Substituted γ-Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis
  作者：Jiajia Ma、Jiahui Lin、Lifang Zhao、Klaus Harms、Michael Marsch、Xiulan Xie、Eric Meggers

  DOI：10.1002/anie.201804040

  日期：2018.8.27

  β‐Substituted chiral γ‐aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of β‐substituted γ‐aminobutyric acid derivatives through visible‐light‐induced photocatalyst‐free asymmetric radical conjugate additions is reported. Various β‐substituted γ‐aminobutyric

  β-取代的手性γ-氨基丁酸具有重要的生物学活性，是合成药物的重要中间体。本文报道了通过无可见光诱导的无光催化剂不对称自由基共轭物加成反应合成β-取代的γ-氨基丁酸衍生物的有效催化对映选择性方法。以良好的收率（42–89％）和出色的对映选择性（90-97％ee）获得了各种β-取代的γ-氨基丁酸类似物，包括以前难以获得的含氟化季铵立体中心的衍生物。通过提供直接合成的药物或相关生物活性化合物（S）-普瑞巴林（）的合成途径，证明了有价值的应用R）-baclofen，（R）-咯利普兰和（S）-nebracetam。
• Acyloxyalkyl carbamate prodrugs, methods of synthesis and use
  申请人：Gallop A. Mark

  公开号：US20050107334A1

  公开（公告）日：2005-05-19

  The disclosures herein relate generally to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The disclosures herein also relate to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.

  本文涉及的内容通常与(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的酰氧基烷基氨基甲酸酯前药、其制药组合物、制备(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的前药的方法、使用(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的前药的方法，以及治疗或预防常见疾病和/或疾病，如痉挛和/或酸反流病的制药组合物。本文还涉及适用于口服和口服缓释剂型的(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的酰氧基烷基氨基甲酸酯前药。
• ACYLOXYALKYL CARBAMATE PRODRUGS, METHODS
  申请人：Gallop Mark A.

  公开号：US20090234138A1

  公开（公告）日：2009-09-17

  The disclosures herein relate generally to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The disclosures herein also relate to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.

  本文披露了关于(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的酰氧基烷基氨基甲酸酯前药、其制药组合物、制备(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的前药的方法、使用(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的前药的方法，以及用于治疗或预防普通疾病和/或紊乱，如痉挛和/或酸反流病的制药组合物。本文还涉及适用于口服的(±)-4-氨基-3-(4-氯苯基)丁酸及其类似物的酰氧基烷基氨基甲酸酯前药以及其持续释放口服剂型。
• ACYLOXYALKYL CARBAMATE PRODRUGS, METHODS OF SYNTHESIS AND USE
  申请人：Gallop A. Mark

  公开号：US20080096960A1

  公开（公告）日：2008-04-24

  The disclosures herein relate generally to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The disclosures herein also relate to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.

  本文涉及到(±)-4-氨基-3-(4-氯苯基)丁酸和其类似物的酰氧基烷基氨基甲酸酯前药、其制药组合物、制备(±)-4-氨基-3-(4-氯苯基)丁酸和其类似物的前药的方法、使用(±)-4-氨基-3-(4-氯苯基)丁酸和其类似物的前药的方法，以及其制药组合物用于治疗或预防常见疾病和/或疾病，如痉挛和/或酸逆流病。本文还涉及适用于口服的酰氧基烷基氨基甲酸酯前药和其持续释放口服剂型。