(2R,4R)-4-hydroxy-2-hydroxymethyl-1-(4-tolylsulfonyl)pyrrolidine | 57850-05-2

• 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: (2R,4R)-4-hydroxy-2-hydroxymethyl-1-(4-tolylsulfonyl)pyrrolidine
• 英文别名: cis-4-Hydroxy-N-tosyl-D-prolinol；(3R,5R)-5-(hydroxymethyl)-1-(4-methylphenyl)sulfonylpyrrolidin-3-ol
• CAS: 57850-05-2
• 化学式: C₁₂H₁₇NO₄S
• 分子量: 271.337
• InChiKey: RBSLQBNFZCEBJT-GHMZBOCLSA-N

物化性质

• 熔点：
  76-79 °C
• 沸点：
  468.6±55.0 °C(Predicted)
• 密度：
  1.364±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4R)-4-hydroxy-2-hydroxymethyl-1-(4-tolylsulfonyl)pyrrolidine 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 sodium azide 、 氢溴酸 、 氢气 、 potassium carbonate 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 116.67h， 生成 7-((2S,4R)-4-Amino-2-methyl-pyrrolidin-1-yl)-1-tert-butyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones

  摘要：

  A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3-carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.

  DOI：

  10.1021/jm00100a028
• 作为产物：
  描述：

  顺式-4-羟基-D-脯氨酸盐酸盐 在 sodium hydroxide 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 39.0h， 生成 (2R,4R)-4-hydroxy-2-hydroxymethyl-1-(4-tolylsulfonyl)pyrrolidine
  参考文献：
  名称：

  Synthesis of (1R,4R)- and (1S,4S)-2,5-Diazabicyclo[2.2.1]heptanes and TheirN-Substituted Derivatives

  摘要：

  (1R,4R)-和(1S,4S)-2,5-二氮杂双环[2.2.1]庚烷环系的衍生物以对映体纯形式从反式-4-羟基-L-脯氨酸（2）中制备而成。目标化合物是抗菌喹啉羧酸的前体。

  DOI：

  10.1055/s-1990-27056

文献信息

• Copper-Catalyzed Enantioselective Aerobic Alkene Aminooxygenation and Dioxygenation: Access to 2-Formyl Saturated Heterocycles and Unnatural Proline Derivatives
  作者：Raul L. L. Carmo、Samuel L. Galster、Tomasz Wdowik、Chaeeon Song、Sherry R. Chemler

  DOI：10.1021/jacs.3c01985

  日期：2023.6.28

  Alkene aminooxygenation and dioxygenation reactions that result in carbonyl products are uncommon, and protocols that control absolute stereochemistry are rare. We report herein catalytic enantioselective alkene aminooxygenation and dioxygenation that directly provide enantioenriched 2-formyl saturated heterocycles under aerobic conditions. Cyclization of substituted 4-pentenylsulfonamides, catalyzed

  产生羰基产物的烯烃氨基氧化和双氧化反应并不常见，控制绝对立体化学的方案也很少。我们在此报道了催化对映选择性烯烃氨基氧化和双氧化，其在有氧条件下直接提供对映体富集的2-甲酰基饱和杂环。由容易获得的手性铜配合物催化并采用分子氧作为氧源和化学计量氧化剂，取代的4-戊烯基磺酰胺的环化可直接有效地提供手性2-甲酰基吡咯烷。这些醛的还原或氧化后处理提供它们各自的氨基醇或氨基酸（非天然脯氨酸）。还证明了二氢吲哚和异喹啉的对映选择性合成。同时，各种烯醇在类似条件下环化提供2-甲酰基四氢呋喃、酞烷、异色满和吗啉。铜配体的性质、分子氧的浓度和反应温度都会影响产物的分布。手性氮和氧杂环是生物活性小分子的常见成分，这些使能技术提供了用即用型羰基亲电子试剂功能化的饱和杂环。
• JORDIS, ULRICH;SAUTER, FRITZ;SIDDIG, SUHAIB M.;KUENBURG, BERNHARD;BHATTAC+, SYNTHESIS, # 10,(1990) N0, C. 925-930
  作者：JORDIS, ULRICH、SAUTER, FRITZ、SIDDIG, SUHAIB M.、KUENBURG, BERNHARD、BHATTAC+

  DOI：——

  日期：——
• Preparation of diazabicyclic intermediates
  申请人：PFIZER INC.

  公开号：EP0397351B1

  公开（公告）日：1994-07-20
• Synthesis of (1<i>R</i>,4<i>R</i>)- and (1<i>S</i>,4<i>S</i>)-2,5-Diazabicyclo[2.2.1]heptanes and Their<i>N</i>-Substituted Derivatives
  作者：Ulrich Jordis、Fritz Sauter、Suhaib M. Siddiqi、Bernhard Küenburg、Kaberi Bhattacharya

  DOI：10.1055/s-1990-27056

  日期：——

  Derivatives of the (1R,4R)- and (1S,4S)-2,5-diazabicyclo- [2.2.1]heptane ring system are prepared in enantiomerically pure form from trans-4-hydroxy-L-proline (2). The target compounds are precursors of antibacterial quinolone carboxyclic acids.

  (1R,4R)-和(1S,4S)-2,5-二氮杂双环[2.2.1]庚烷环系的衍生物以对映体纯形式从反式-4-羟基-L-脯氨酸（2）中制备而成。目标化合物是抗菌喹啉羧酸的前体。
• Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones
  作者：P. Di Cesare、D. Bouzard、M. Essiz、J. P. Jacquet、B. Ledoussal、J. R. Kiechel、P. Remuzon、R. E. Kessler、J. Fung-Tomc、J. Desiderio

  DOI：10.1021/jm00100a028

  日期：1992.10

  A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3-carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.