(2S,5S)-1-<(S)-1-Phenylethyl>-2,5-bis(hydroxymethyl)pyrrolidine | 148773-68-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2S,5S)-1-<(S)-1-Phenylethyl>-2,5-bis(hydroxymethyl)pyrrolidine
• 英文别名: (2S,5S)-2,5-bis(hydroxymethyl)-1-((S)-1-phenylethyl)pyrrolidine；[(2S,5S)-5-(hydroxymethyl)-1-[(1S)-1-phenylethyl]pyrrolidin-2-yl]methanol
• CAS: 148773-68-6
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: MHBLCGJNTLFFBE-UBHSHLNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,5S)-1-<(S)-1-Phenylethyl>-2,5-bis(hydroxymethyl)pyrrolidine 在 palladium dihydroxide 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 (S,S)-trans-2,5-bis(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  A Formal [3 + 3] Cycloaddition Reaction. 5. An Enantioselective Intramolecular Formal Aza-[3 + 3] Cycloaddition Reaction Promoted by Chiral Amine Salts

  摘要：

  A detailed account on chiral secondary amine salt promoted enantioselective intramolecular formal aza-[3 + 3] cycloadditions is described here for the first time. The dependence of enantioselectivity on the structural feature of these chiral amines is thoroughly investigated. This study also reveals a very interesting reversal of the stereochemistry in the respective cycloadducts obtained using C-1- and C-2-symmetric amine salts. In addition, the influence of solvents, counteranions, and temperatures on the enantioselectivity is described, and a unified mechanistic model based on experimental results as well as semiempirical calculations is proposed.

  DOI：

  10.1021/jo050171s
• 作为产物：
  描述：

  1-<(S)-1-Phenylethyl>-2,5-cis-bis(methoxycarbonyl)pyrrolidine 在 lithium aluminium tetrahydride 、 sodium methylate 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 6.5h， 生成 (2S,5S)-1-<(S)-1-Phenylethyl>-2,5-bis(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  A Convenient Synthesis of Enantiomeric Pairs of 2,5-Disubstituted Pyrrolidines of C₂-Symmetry

  摘要：

  通过使用 (-)-1-苯基乙胺作为手性辅助剂，从二甲基阳离子-2,5-二溴己二酸酯制备了三种二叠体异构体的 2,5-双(甲氧基羧基)吡咯烷衍生物，并通过结晶和涉及立体选择性水解的色谱分离进行分离。收回顺式异构体并使其异构化为反式异构体。从每种反式异构体出发，通过一种简短的路线合成了具有 C2 对称性的光学活性 2,5-二取代的 [2,5-双(甲氧基甲基)和 2,5-双(甲氧基甲氧基甲基)] 吡咯烷。

  DOI：

  10.1055/s-1993-25852

文献信息

• VLA-4 INHIBITORY DRUG
  申请人：Machinaga Nobuo

  公开号：US20090233901A1

  公开（公告）日：2009-09-17

  There is provided a VLA-4 inhibitory drug having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally. A compound represented by the following formula (I): wherein R 1 represents a hydrogen atom or a C1-8 alkyl group; R 2 represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group, or a benzyloxy group which may be substituted; Q represents a monocyclic or bicyclic nitrogen-containing heterocyclic group which may be substituted, and has a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents a bicyclic aromatic hydrocarbon ring group which may be substituted, or a bicyclic aromatic heterocyclic group which may be substituted; R 3a , R 3b and R 3c each independently represent a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; and A 1 represents a nitrogen atom or C—R 3d (wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group), or a salt thereof, or a VLA-4 inhibitory drug comprising the compound or the salt as an active ingredient.

  提供了一种VLA-4抑制剂药物，具有良好的口服吸收性，并在口服给药时表现出足够的抗炎效果。其中，化合物的表示式如下（I）：其中，R1表示氢原子或C1-8烷基；R2表示氢原子、卤素原子、C1-8烷氧基或可取代的苄氧基；Q表示可取代的单环或双环含氮杂环基团，并具有氮原子作为键合位点；Y表示氧原子或CH2；W表示可取代的双环芳香烃环基团或可取代的双环芳香杂环基团；R3a、R3b和R3c分别独立地表示氢原子、卤素原子、C1-8烷氧基或C1-8烷基；A1表示氮原子或C-R3d（其中，R3d表示氢原子、卤素原子、C1-8烷氧基或C1-8烷基），或其盐，或包含该化合物或其盐作为活性成分的VLA-4抑制剂药物。
• VLA-4 inhibitory drug
  申请人：Machinaga Nobuo

  公开号：US20130065882A1

  公开（公告）日：2013-03-14

  This invention relates to a VLA-4 inhibitory drug, having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally, wherein an active ingredient is represented by formula (I), or a salt thereof: Q represents an optionally-substituted monocyclic or bicyclic nitrogen-containing heterocyclic group having a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents an optionally-substituted bicyclic aromatic hydrocarbon ring group or an optionally-substituted bicyclic aromatic heterocyclic group; A 1 represents a nitrogen atom or C—R 3d wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; R 1 represents H or a C1-8 alkyl group; R 2 represents H, a halogen, a C1-8 alkoxy

  本发明涉及一种VLA-4抑制剂药物，具有良好的口服吸收性，并在口服给药时展现足够的抗炎效果，其中活性成分由公式（I）或其盐表示： Q代表一个可选取代的含氮杂环基团，其为单环或双环结构，其中氮原子为键合位点； Y代表一个氧原子或CH2； W代表一个可选取代的双环芳香烃环基团或可选取代的双环芳香杂环基团； A1代表一个氮原子或C-R3d，其中R3d代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团； R1代表氢原子或C1-8烷基团； R2代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团。
• C2-Symmetric Pyrrolidine-Based Chiral Ammonium Salts as a Phase-Transfer Catalyst
  作者：Takashi Itoh、Tatsuya Ishikawa、Kazuhiro Nagata、Sachiko Kani、Mamoru Matsuo、Daisuke Sano、Takuya Kanemitsu、Michiko Miyazaki

  DOI：10.3987/com-11-12254

  日期：——

  Chiral pyrrolidinium salts having substituents at the alpha, alpha' positions were synthesized to develop a chiral phase-transfer catalyst which have more simplified structure. The catalytic function of these synthesized catalysts was evaluated using asymmetric benzylation of N-(diphenylmethylene)glycine tert-butyl ester, and alpha,alpha'-disubstituded pyrrolidinium salts having an alkyl chain with a hydroxyl group at a chiral center were found to afford moderate enantioselectivity.
• US8129366B2
  申请人：——

  公开号：US8129366B2

  公开（公告）日：2012-03-06
• A Convenient Synthesis of Enantiomeric Pairs of 2,5-Disubstituted Pyrrolidines of C₂-Symmetry
  作者：Yukio Yamamoto、Jun'ichi Hoshino、Yukiko Fujimoto、Junko Ohmoto、Seiji Sawada

  DOI：10.1055/s-1993-25852

  日期：——

  By the use of (-)-1-phenylethylamine as a chiral auxiliary, three diastereomeric isomers of 2,5-bis(methoxycarbonyl)pyrrolidine derivatives are prepared from dimethyl rac-2,5-dibromoadipate and separated by crystallization and chromatographic fractionation involving stereoselective hydrolysis. The cis isomer is recovered and epimerized to the trans counterparts. Starting from each of the two trans isomers, optically active 2,5-disubstituted [2,5-bis(methoxymethyl) and 2,5-bis(methoxymethoxymethyl)] pyrrolidines of C 2-symmetry are synthesized by a short route.

  通过使用 (-)-1-苯基乙胺作为手性辅助剂，从二甲基阳离子-2,5-二溴己二酸酯制备了三种二叠体异构体的 2,5-双(甲氧基羧基)吡咯烷衍生物，并通过结晶和涉及立体选择性水解的色谱分离进行分离。收回顺式异构体并使其异构化为反式异构体。从每种反式异构体出发，通过一种简短的路线合成了具有 C2 对称性的光学活性 2,5-二取代的 [2,5-双(甲氧基甲基)和 2,5-双(甲氧基甲氧基甲基)] 吡咯烷。