N-benzyl-2,5-bis(hydroxymethyl)pyrrolidine

• 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: N-benzyl-2,5-bis(hydroxymethyl)pyrrolidine
• 英文别名: trans-2,5-bis(hydroxymethyl)pyrrolidine；[(2S,5S)-1-benzyl-5-(hydroxymethyl)pyrrolidin-2-yl]methanol
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: KDHJNPHFSBLEMM-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 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：

  N-benzyl-2,5-bis(hydroxymethyl)pyrrolidine 在 Pseudomonas cepacia lipase (lipase Amano PS) 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 2.0h， 生成 (+)-(2R,5R)-N-benzyl-2,5-bis(acetoxymethyl)pyrrolidine
  参考文献：
  名称：

  脂肪酶催化转 2,5-二取代吡咯烷的酯交换反应：取代基对对映选择性的影响

  摘要：

  已经研究了使用脂肪酶催化的酯交换对外消旋 N-芳基甲基化反式-2-乙酰氧基-甲基-5-羟甲基吡咯烷的动力学拆分。对映选择性显着取决于芳环的结构，并且发现 N-3,5-二甲基苄基吡咯烷是本反应的最佳底物。

  DOI：

  10.1246/cl.1998.1231
• 作为产物：
  描述：

  trans-2,5-dimethyl N-benzylpyrrolidine-2,5-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到N-benzyl-2,5-bis(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  C 2对称反式-2,5-双（羟甲基）吡咯烷的两种对映体的合成。脂肪酶介导的顺序动力学拆分

  摘要：

  脂肪酶介导的顺序动力学拆分已被用于以光学纯的形式给出反式-2,5-双（羟甲基）吡咯烷的两种对映异构体。还报告了这些分辨率中不同参数对ee和产量的影响。

  DOI：

  10.1016/s0040-4039(00)73281-3

文献信息

• A facile synthesis of optically active C2-symmetric 2,5-disubstituted pyrrolidines and other β,β′-dihydroxyamines
  作者：Kevin Koh、Robert N. Ben、T. Durst

  DOI：10.1016/0040-4039(94)85057-7

  日期：1994.1

  has been converted into the di-(R)-pantolactone ester of (S,S)-pyyrolidine-2,5-dicarboxylic acid in two steps. This compound serves as a precursor to C2-symmetric 2,5-disubstituted pyrrolidines. The synthesis of linear C2-symmetric β,β′-dihydroxyamines starting with α-bromophenylacetic acid and (S)-phenylglycine ethyl ester is also reported.

  2，5-二溴己二酸已分两步转化为（S，S）-吡咯烷-2,5-二羧酸的二-（R）-泛内酯。该化合物用作C 2对称的2，5-二取代的吡咯烷的前体。还报道了以α-溴苯基乙酸和（S）-苯基甘氨酸乙酯为起始原料的线性C 2对称β，β'-二羟基胺的合成。
• Lipase-catalyzed kinetic resolution of trans-2,5-disubstituted pyrrolidine derivatives
  作者：Yasuhiro Kawanami、Hitoko Moriya、Yuka Goto、Keiko Tsukao、Michihiro Hashimoto

  DOI：10.1016/0040-4020(95)00907-8

  日期：1996.1

  Enantioselective preparation of C2-symmetric (−)-(2S,5S)-N-benzyl-trans-2,5-bis(acetoxymethyl)pyrrolidine was carried out by the lipase-catalyzed hydrolysis of racemic diacetate. Organic co-solvent affected the enantioselectivity and 50% DMSO in the phosphate buffer was found to be the optimal solvent system. A possible active site model was also described.

  通过脂肪酶催化的外消旋二乙酸酯的水解进行C 2对称（-）-（2S，5S）-N-苄基-反式-2，5-双（乙酰氧基甲基）吡咯烷的对映选择性制备。有机助溶剂会影响对映选择性，磷酸盐缓冲液中的50％DMSO被认为是最佳的溶剂体系。还描述了可能的活动站点模型。
• [EN] OXAZEPINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS D'OXAZÉPINE ET LEURS UTILISATIONS DANS LE TRAITEMENT DU CANCER
  申请人：GENENTECH INC

  公开号：WO2022216762A1

  公开（公告）日：2022-10-13

  Provided herein are acyclic oxazepinyl compounds useful in the treatment on cancers.

  本文提供了一些用于治疗癌症的非环状噁唑啉化合物。
• Lipase-Catalyzed Kinetic Resolution of<i>trans</i>-2,5-Disubstituted Pyrrolidine Derivatives
  作者：Yasuhiro Kawanami、Hitoko Moriya、Yuka Goto

  DOI：10.1246/cl.1994.1161

  日期：1994.7

  Enantioselective preparation of (−)-(2S,5S)-N-benzyl-trans-2,5-bis(acetoxymethyl)pyrrolidine was carried out by the lipase-catalyzed hydrolysis of racemic diacetate in phosphate buffer contained 20% DMSO.

  (-)-(2S,5S)-N-苄基-反式-2,5-双(乙酰氧基甲基)吡咯烷的对映选择性制备是通过脂肪酶催化的外消旋二乙酸酯在含有20% DMSO的磷酸盐缓冲液中水解来进行的。
• Symmetry-Assisted Synthesis of <i>C</i>₂-Symmetric <i>trans</i>-α,α‘-Bis(hydroxymethyl)pyrrolidine and -piperidine Derivatives via Double Sharpless Asymmetric Dihydroxylation of α,ω-Terminal Dienes
  作者：Hiroki Takahata、Seiki Takahashi、Shin-ichi Kouno、Takefumi Momose

  DOI：10.1021/jo971995f

  日期：1998.4.1

  A new strategy has been developed for the synthesis of C-2-symmetric trans-alpha,alpha'-bis(hydroxymethyl)pyrrolidine and piperidine derivatives 1-3 starting from symmetric alpha,omega-terminal dienes 4-6. The double-asymmetric dihydroxylation (AD) reaction of 4-6 gave C-2-symmetric tetrols, which were converted in a four-step sequence to C-2-symmetric azacycloalkanes 17, 9, and 22, respectively. These azacycloalkanes were transformed into 1-3 in high enantiomeric excess (82% --> 98%ee). The double AD reaction proved to cause enantiomeric enhancement, even though the asymmetric induction for the first AD reaction is moderate. In addition, it was observed that the chromatography on silica gel of several C-2-symmetric azacycloalkanes (17, 20, and 22) of varying ee's resulted in marked enantiomeric fractionation.