(2S,4R)-N-acetyl-4-methoxy-2-(methoxymethyl)pyrrolidine | 1372810-13-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S,4R)-N-acetyl-4-methoxy-2-(methoxymethyl)pyrrolidine
• 英文别名: 1-[(2S,4R)-4-methoxy-2-(methoxymethyl)pyrrolidin-1-yl]ethanone
• CAS: 1372810-13-3
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: RVPMUDQXXANUFC-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,4R)-N-acetyl-4-methoxy-2-(methoxymethyl)pyrrolidine 在 盐酸 作用下， 以 水 为溶剂， 反应 15.0h， 以95.6%的产率得到(2S,4R)-4-methoxy-2-(methoxymethyl)pyrrolidine hydrochloride
  参考文献：
  名称：

  衍生自反式-4-羟基-L-脯氨酸的新型光学活性 4-烷氧基脯氨醇醚

  摘要：

  (2S,4R)-trans-4-Hydroxy-L-proline 已被用作手性池源，用于有效合成光学活性保护的 4-羟基脯氨醇。N-酰基保护和酯形成后，引入第一个醚部分，保持与酯相邻的手性中心。然后，酯的还原产生相应的甲醇，必须选择性地将其烷基化以避免与 N-保护基团发生副反应。最后，去除 N-酰基官能团以生成显示定义取代模式的目标甲基和叔丁基醚。如此形成的旋光4-烷氧基脯氨醇醚可用作生物活性化合物中的核心片段或用作合适起始材料中的稳定手性辅助亚单元。

  DOI：

  10.1002/ejoc.201101156
• 作为产物：
  描述：

  trans-N-acetyl-4-hydroxyprolinol 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以2.65 g的产率得到(2S,4R)-N-acetyl-4-methoxy-2-(methoxymethyl)pyrrolidine
  参考文献：
  名称：

  衍生自反式-4-羟基-L-脯氨酸的新型光学活性 4-烷氧基脯氨醇醚

  摘要：

  (2S,4R)-trans-4-Hydroxy-L-proline 已被用作手性池源，用于有效合成光学活性保护的 4-羟基脯氨醇。N-酰基保护和酯形成后，引入第一个醚部分，保持与酯相邻的手性中心。然后，酯的还原产生相应的甲醇，必须选择性地将其烷基化以避免与 N-保护基团发生副反应。最后，去除 N-酰基官能团以生成显示定义取代模式的目标甲基和叔丁基醚。如此形成的旋光4-烷氧基脯氨醇醚可用作生物活性化合物中的核心片段或用作合适起始材料中的稳定手性辅助亚单元。

  DOI：

  10.1002/ejoc.201101156

文献信息

• METHOD FOR SYNTHESIS OF REACTIVE CONJUGATE CLUSTERS
  申请人：Ionis Pharmaceuticals, Inc.

  公开号：EP3811977A1

  公开（公告）日：2021-04-28

  Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods. The reactive conjugate cluster has the formula: (L-A-N(H)C(=O)-E-)m-Bga wherein: L is a ligand; A is C2 to C10 alkyl optionally interrupted with one or more groups selected from -O-, -N(H)- and C(=O); E is a single bond or C1 to C10 alkyl optionally interrupted with one or more groups selected from -O-, -N(H)-and C(=O); Bga is a reactive branching group; m is from 2 to 6 - and C(=O); m is from 2 to about 6;

  本文提供了用于合成活性共轭簇的改进方法以及用于此类方法的中间体。特别是，本文提供的改进方法通过减少所需合成步骤的数量，提高了活性共轭簇的合成效率。使用改进方法制备的活性共轭簇不包括使用现有方法形成的任何反式酰化杂质。与现有方法相比，改进方法还能提高总体产量和成本效益。 活性共轭团簇的化学式为 (L-A-N(H)C(=O)-E-)m-Bga 其中 L 是配体； A 是选自-O-、-N(H)-和 C(=O)的一个或多个基团任选间断的 C2 至 C10 烷基； E 是单键或 C1 至 C10 烷基，可选择被一个或多个选自-O-、-N（H）- 和 C（=O）的基团打断 选自-O-、-N(H)-和 C(=O)的一个或多个基团； Bga 是活性分支基团； m 为 2 至 6 - 和 C（＝O）；m 为 2 至约 6；
• Methods for true isothermal strand displacement amplification
  申请人：ELITechGroup, Inc.

  公开号：US10975423B2

  公开（公告）日：2021-04-13

  Methods, primers and probes are provided for the isothermal amplification and detection, without denaturation, of double stranded nucleic acid targets for polymerase strand displacement amplification (“iSDA”). The methods and compositions disclosed are highly specific for nucleic acid targets with high sensitivity, specificity and speed that allow detection of clinical relevant target levels. The methods and compositions can easily be used to amplify or detect nucleic acid targets in biological samples.

  提供了用于聚合酶链位移扩增（"iSDA"）的双链核酸靶标的等温扩增和检测方法、引物和探针，无需变性。所公开的方法和组合物对核酸靶标具有高度特异性，灵敏度高、特异性强、速度快，可检测临床相关的靶标水平。这些方法和组合物可轻松用于扩增或检测生物样本中的核酸靶标。
• METHODS FOR TRUE ISOTHERMAL STRAND DISPLACEMENT AMPLIFICATION
  申请人：ELITechGroup, Inc.

  公开号：US20200040387A1

  公开（公告）日：2020-02-06

  Methods, primers and probes are provided for the isothermal amplification and detection, without denaturation, of double stranded nucleic acid targets for polymerase strand displacement amplification (“iSDA”). The methods and compositions disclosed are highly specific for nucleic acid targets with high sensitivity, specificity and speed that allow detection of clinical relevant target levels. The methods and compositions can easily be used to amplify or detect nucleic acid targets in biological samples.
• Modified RNA Agents with Reduced Off-Target Effect
  申请人：ALNYLAM PHARMACEUTICALS, INC.

  公开号：US20220290145A1

  公开（公告）日：2022-09-15

  One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2′-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.
• [EN] MODIFIED RNA AGENTS WITH REDUCED OFF-TARGET EFFECT<br/>[FR] AGENTS ARN MODIFIÉS À EFFET HORS CIBLE RÉDUIT
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2018098328A1

  公开（公告）日：2018-05-31

  One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2'-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.