(3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate | 116143-02-3

• 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: (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate
• 英文别名: (3R)-3-acetoxy-1-(phenylmethyl)pyrrolidine；(3R)-1-benzyl-3-acetatoxypyrrolidine；(3R)-N-benzyl-3-acetoxy-pyrrolidine；(R)-1-benzylpyrrolidin-3-yl acetate；(R)-N-benzyl-3-pyrrolidinyl acetate；(R)-3-acetyloxy-1-phenylmethyl pyrrolidine；[(3R)-1-benzylpyrrolidin-3-yl] acetate
• CAS: 116143-02-3
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: WAZGGSCOYCPXGS-CYBMUJFWSA-N

物化性质

• 沸点：
  292.1±33.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate 在 吡啶 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 72.0h， 生成 (S)-1-Benzyl-N,N-dimethylpyrrolidin-3-amine
  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：

  苄胺 在 吡啶 、 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 23.0h， 生成 (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate
  参考文献：
  名称：

  3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: Inhibition of rat intestinal α-glucosidase

  摘要：

  Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of a-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 +/- 0.046 and a K-I of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of similar to 90 degrees of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity.Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.04.007

文献信息

• Exploring Derivatives of Quinazoline Alkaloid <scp>l</scp>-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors
  作者：Mudassier Ahmad、Mushtaq A. Aga、Javeed Ahmad Bhat、Brijesh Kumar、Abdul Rouf、Neena Capalash、Mubashir Javeed Mintoo、Ashok Kumar、Priya Mahajan、Dilip Manikrao Mondhe、Amit Nargotra、Parduman Raj Sharma、Mohmmad Afzal Zargar、Ram A. Vishwakarma、Bhahwal Ali Shah、Subhash Chandra Taneja、Abid Hamid

  DOI：10.1021/acs.jmedchem.7b00322

  日期：2017.4.27

  inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency

  1- Vasicine是一种喹唑啉生物碱，具有电子致密环，并且在其结构中具有其他功能。利用基于计算机模拟研究的靶向定向合成（TOS），合成了具有显着对接分数的分子，其中包含1- vasicine的不同衍生物作为帽。有趣的是，发现一个分子，即4a，它含有3-羟基吡咯烷作为帽基和一个六碳长的脂肪族链作为连接基，可以抑制HDAC。图4a显示了对I类HDAC同工型的更多特异性。与癌细胞系相比，还发现4a对正常细胞系的细胞毒性较小。4a通过多种机制抑制癌细胞的生长并诱导细胞死亡。但是，发现4a可以诱导细胞死亡而与ROS的产生无关，并且与许多基于天然产物的HDAC抑制剂不同，发现4a在体内条件下是无毒的。重要的是，我们首次报道了使用3-羟基吡咯烷帽合成具有良好效力的HDAC抑制剂的可能性。
• An Efficient Dynamic Kinetic Resolution of N-Heterocyclic 1,2-Amino Alcohols
  作者：Richard Lihammar、Renaud Millet、Jan-E. Bäckvall

  DOI：10.1002/adsc.201100466

  日期：2011.9

  A chemoenzymatic dynamic kinetic resolution (DKR) of N‐heterocyclic amino alcohols is described. Various lipases were studied as biocatalysts for the kinetic resolution of N‐heterocyclic 1,2‐amino alcohols. The influence of the support of the enzymes on the enantioselectivity in the resolution of different substrates is highlighted. Various 3‐acetoxypyrrolidines and ‐piperidines were obtained in high

  描述了N杂环氨基醇的化学酶动力学动力学拆分（DKR）。研究了各种脂肪酶作为生物催化剂，用于动力学拆分N-杂环1,2-氨基醇。强调了酶的支持对不同底物的拆分中对映选择性的影响。在有效的DKR反应中，以高收率和高对映体过量获得了各种3-乙酰氧基吡咯烷和哌啶。
• Enzymatic Optical Resolution of<i>N</i>-Benzyl-3-pyrrolidinol
  作者：Akira Horiguchi、Ken-ichi Mochida

  DOI：10.1271/bbb.59.1287

  日期：1995.1

  The enzymatic optical resolution of racemic N-benzyl-3-pyrrolidinol (2) was investigated. It was found that only (R)-2 was acetylated by the lipase Amano P in yields of 50% and 100%e.e. Remaining (S)-alcohol 2 could be chemically inverted to (R)-acetate 3. A continuous reaction in a column reactor could be also applied to this optical resolution. After concentrating the eluted solution, the residue was subjected to the inversion reaction to provide (R)-acetate 3 in an 83% yield and 91%e.e. from the racemate.

  研究了外消旋 N-苄基-3-吡咯烷醇（2）的酶光学分解。研究发现，只有(R)-2 能被脂肪酶 Amano P 乙酰化，乙酰化率分别为 50%和 100%，即剩余的(S)-醇 2 可以通过化学反应转化为(R)-乙酸酯 3。柱式反应器中的连续反应也可用于这种光学分解。浓缩洗脱溶液后，残留物进行反转反应，得到(R)-乙酸酯 3，收率为 83%，外消旋体的反应效率为 91%e.e.。
• Natural (−)-Vasicine as a Novel Source of Optically Pure 1-Benzylpyrrolidin-3-ol
  作者：Mushtaq A. Aga、Brijesh Kumar、Abdul Rouf、Bhahwal A. Shah、Samar S. Andotra、Subhash C. Taneja

  DOI：10.1002/hlca.201200307

  日期：2013.5

  A facile and scalable methodology for the preparation of optically active (3S)‐1‐benzylpyrrolidin‐3‐ol (3), an important drug precursor, is reported. Starting from the naturally occurring alkaloid (−)‐vasicine (1), a major alkaloid of the plant Adhatoda vasica, 3 was obtained in 84% overall yield (Scheme 3).

  据报道，一种重要的药物前体光学活性（3 S）-1-苄基吡咯烷酮3-ol（3）的制备方法简便易行。（ - ） -选自天然存在的生物碱开始vasicine（1），一个大工厂的生物碱藏药vasica，3在84％的总收率（获得方案3）。
• PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES
  申请人：Taneja Subhash Chandra

  公开号：US20120101285A1

  公开（公告）日：2012-04-26

  The present invention relates to a facile, highly efficient and economical process for the preparation of optically active N-benzyl-3-hydroxypyrrolidine in high yield from a naturally occurring alkaloid vasicine. The natural alkaloid vasicine is used as a precursor of (S)—N-benzyl-3-hydroxypyrrolidine and (R)—N-benzyl-3-hydroxypyrrolidines which can easily be sourced from the medicinal plant Adatoda vasica by the method known in the art and transformed to optical isomers (R) and (S)—N-benzyl-3-hydroxypyrrolidine by the method described in the present invention.

  本发明涉及一种简便、高效、经济的方法，用于从天然生物碱vasicine中高产得到光学活性的N-苄基-3-羟基吡咯烷。天然生物碱vasicine被用作(S)-N-苄基-3-羟基吡咯烷和(R)-N-苄基-3-羟基吡咯烷的前体，这些可通过已知的方法从药用植物Adatoda vasica中轻易获取，并通过本发明中所述的方法转化为光学异构体(R)和(S)-N-苄基-3-羟基吡咯烷。