benzyl (2R,4R)-2-ethyl-4-methylpyrrolidine-1-carboxylate | 1388191-71-6

• 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: benzyl (2R,4R)-2-ethyl-4-methylpyrrolidine-1-carboxylate
• CAS: 1388191-71-6
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: URKYRHRDMGEZDO-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (R)-hex-5-en-3-amine 在 sodium tetrahydroborate 、 20 % Pd(OH)2/C 、 氢气 、 potassium carbonate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.0h， 生成 benzyl (2R,4R)-2-ethyl-4-methylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of Enantiopure 5-Substituted 2,3-Methanopyrrolidines by Cyclization of Enantiopure α-Branched α-N-Homoallylamino Nitriles

  摘要：

  The preparation of 5-substituted 2,3-methanopyrrolidines by the stereoselective cyclization of zincated alpha-amino nitriles derived from enantiopure alpha-branched homoallylamines has been investigated. The formation of trans adducts in excellent diastereoselectivities (up to > 98:2) and good yields (up to 71%) is observed. The absolute configuration and enantiomeric excess are dependent on the nitrogen protecting group.

  DOI：

  10.1055/s-0031-1291046

文献信息

• MODIFIED iRNA AGENTS
  申请人：MANOHARAN Muthiah

  公开号：US20100076056A1

  公开（公告）日：2010-03-25

  The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.

  本发明涉及iRNA剂，其中最好包括一个单体，其中核糖基团已被替换为除核糖以外的基团，并进一步包括一个具有一个或多个连接基团的连接件，其中至少一个连接基团是可切断的连接基团。连接件反过来可以连接到所选的基团，例如，配体，例如，靶向或传递基团，或改变物理性质的基团。可切断的连接基团是足够稳定的连接基团，以便在细胞外定向治疗有益量的iRNA剂（例如，单链或双链iRNA剂），通过可切断的连接基团与靶向剂结合，以靶向细胞，但在进入靶细胞后被切断以释放iRNA剂从靶向剂中。包括这样一个单体可以允许调节iRNA剂的一个性质，将其纳入其中，例如，通过使用非核糖基团作为配体或其他实体（例如，亲脂性基团，例如，胆固醇）的连接点，直接或间接地连接。本发明还涉及制备和使用这种修改的iRNA剂的方法。
• IRNA AGENTS WITH BIOCLEAVABLE TETHERS
  申请人：MANOHARAN Muthiah

  公开号：US20100267941A1

  公开（公告）日：2010-10-21

  The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

  本发明涉及iRNA代理，它们包括一个单体，其中核糖基团已被替换为其他核糖基团，进一步包括一个具有一个或多个连接基团的连接体，其中至少一个连接基团是可裂解的连接基团。 连接体反过来可以连接到所选的基团，例如配体，例如靶向或递送基团，或改变物理性质的基团。 可裂解的连接基团足够稳定，使其允许将治疗上有益的iRNA代理（例如单链或双链iRNA代理）通过可裂解的连接基团耦合到靶向剂，以靶向细胞，但进入目标细胞后会裂解以释放iRNA代理。
• iRNA AGENTS WITH BIOCLEAVABLE TETHERS
  申请人：Alnylam Pharmaceuticals, Inc.

  公开号：US20130281685A1

  公开（公告）日：2013-10-24

  The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

  本发明涉及iRNA代理，其优选包括一个单体，其中核糖基团已被替换为除核糖以外的基团，进一步包括一个具有一个或多个连接基团的缆绳，其中至少一个连接基团是可切断的连接基团。缆绳反过来可以连接到所选的基团，例如配体，例如定向或递送基团，或改变物理性质的基团。可切断的连接基团是足够稳定的连接基团，使其允许通过可切断的连接基团耦合的iRNA代理（例如单链或双链iRNA代理）针对细胞进行治疗上有益的量的靶向，但在进入目标细胞时被切断以释放iRNA代理从定向代理中。
• iRNA AGENTS WITH BIOCLEAVABLE TETHERS
  申请人：Alnylam Pharmaceuticals, Inc.

  公开号：US20150073133A1

  公开（公告）日：2015-03-12

  The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

  本发明涉及iRNA药剂，其中最好包括一个单体，其中核糖基团已被其他核糖以外的基团所取代，该基团还包括一个具有一个或多个连接基团的连接件，其中至少一个连接基团是可断裂的连接基团。连接件可以连接到所选的基团，例如配体，例如靶向或递送基团，或改变物理性质的基团。可断裂的连接基团是足够稳定的连接基团，以在细胞外允许将治疗上有益量的iRNA药剂（例如单链或双链iRNA药剂），通过可断裂的连接基团与靶向剂耦合，以靶向细胞，但在进入靶细胞后被断裂以释放iRNA药剂从靶向剂中。
• US7723509B2
  申请人：——

  公开号：US7723509B2

  公开（公告）日：2010-05-25