3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]propanoic acid | 65595-02-0

• 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: 3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]propanoic acid
• 英文别名: 3-[(2S)-1-[(tert-butoxy)carbonyl]pyrrolidin-2-yl]propanoic acid；3-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]propanoic acid
• CAS: 65595-02-0
• 化学式: C₁₂H₂₁NO₄
• mdl: MFCD11226805
• 分子量: 243.303
• InChiKey: YERVFXLPVTWCHS-VIFPVBQESA-N

物化性质

• 沸点：
  370.9±15.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]propanoic acid 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.33h， 生成 tert-butyl (2S)-2-(4-diazo-3-oxobutyl)-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  Trifluoroacetic acid-mediated intramolecular formal N-H insertion reactions with amino-α-diazoketones: a facile and efficient synthesis of optically pure pyrrolidinones and piperidinones

  摘要：

  三氟乙酸（TFA）被发现促进分子内正式N-H插入反应。经TFA处理后，光学纯的N-Boc-β'-氨基-α-重氮酮（5a-c）和N-Boc-γ'-氨基-α-重氮酮（10a-d）可以保持手性转化为吡咯烷酮（11a-c）和哌啶酮（12a-d），同时去除Boc基团，产率良好至优良。关键词：α-重氮酮，氨基酸，吡咯烷酮，哌啶酮，N-H插入。

  DOI：

  10.1139/v00-066
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 二异丁基氢化铝 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， -78.0~20.0 ℃ 、310.26 kPa 条件下， 反应 33.5h， 生成 3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]propanoic acid
  参考文献：
  名称：

  Trifluoroacetic acid-mediated intramolecular formal N-H insertion reactions with amino-α-diazoketones: a facile and efficient synthesis of optically pure pyrrolidinones and piperidinones

  摘要：

  三氟乙酸（TFA）被发现促进分子内正式N-H插入反应。经TFA处理后，光学纯的N-Boc-β'-氨基-α-重氮酮（5a-c）和N-Boc-γ'-氨基-α-重氮酮（10a-d）可以保持手性转化为吡咯烷酮（11a-c）和哌啶酮（12a-d），同时去除Boc基团，产率良好至优良。关键词：α-重氮酮，氨基酸，吡咯烷酮，哌啶酮，N-H插入。

  DOI：

  10.1139/v00-066

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE
  申请人：WAVE LIFE SCIENCES LTD

  公开号：WO2018237194A1

  公开（公告）日：2018-12-27

  The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

  本公开内容提供了合成技术，包括用于立体选择性合成的试剂和方法。在某些实施例中，本公开内容提供了作为手性辅助剂有用的化合物。在某些实施例中，本公开内容提供了用于寡核苷酸合成的试剂和方法。在某些实施例中，本公开内容提供了用于手性控制寡核苷酸制备的试剂和方法。在某些实施例中，本公开内容的技术特别适用于构建具有挑战性的核苷酸间连接，提供高产率和立体选择性。
• Sequential deprotection–cyclisation reaction: stereoselective synthesis of azabicyclic β-enamino ester derivatives and (−) indolizidine 209D
  作者：Thanasekaran Ponpandian、Shanmugam Muthusubramanian

  DOI：10.1016/j.tet.2012.11.029

  日期：2013.1

  This paper describes a new strategy for the stereoselective synthesis of pyrrolizidine and indolizidine based enamino esters and their acyl derivatives from l-proline. The key reaction in this process involves deprotection followed by ring closure of cyclic N-Boc amino-β-ketoesters. Also, the synthesis of 5R,9R-(−)-indolizidine 209D has been accomplished using this protocol.

  本文描述了一种新的策略，用于从1-脯氨酸立体选择性地合成吡咯烷和吲哚并立定的烯胺酯及其酰基衍生物。该过程中的关键反应包括脱保护，然后关闭环状N -Boc氨基-β-酮酸酯的环。同样，已经使用该方案完成了5 R，9 R -（-）-吲哚并立定209D的合成。
• Synthesis and Antitumor Activity of Novel Dolastatin 10 Analogs.
  作者：Koichi MIYAZAKI、Motohiro KOBAYASHI、Tsugitaka NATSUME、Masaaki GONDO、Takashi MIKAMI、Kyoichi SAKAKIBARA、Shigeru TSUKAGOSHI

  DOI：10.1248/cpb.43.1706

  日期：——

  Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c

  Dolastatin 10（1）是有效的抗肿瘤五肽。合成了各自在组成氨基酸衍生物之一上修饰的新型dolastatin 10类似物，并评估了其对小鼠中P388白血病的抗肿瘤活性。讨论了抗肿瘤活性的结构要求。一些类似物31c，35c，38b和50c在体内显示出出色的活性。选择没有噻唑基团1的高活性50c作为抗肿瘤剂进行进一步开发。
• Structure−Activity Relationship Studies and in Vivo Activity of Guanidine-Based Sphingosine Kinase Inhibitors: Discovery of SphK1- and SphK2-Selective Inhibitors
  作者：Neeraj N. Patwardhan、Emily A. Morris、Yugesh Kharel、Mithun R. Raje、Ming Gao、Jose L. Tomsig、Kevin R. Lynch、Webster L. Santos

  DOI：10.1021/jm501760d

  日期：2015.2.26

  Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that acts as a ligand for five G-protein coupled receptors (S1P(1-5)) whose downstream effects are implicated in a variety of important pathologies including sickle cell disease, cancer, inflammation, and fibrosis. The synthesis of S1P is catalyzed by sphingosine kinase (SphK) isoforms 1 and 2, and hence, inhibitors of this phosphorylation step are pivotal in understanding the physiological functions of SphKs. To date, SphK1 and 2 inhibitors with the potency, selectivity, and in vivo stability necessary to determine the potential of these kinases as therapeutic targets are lacking. Herein, we report the design, synthesis, and structure-activity relationship studies of guanidine-based SphK inhibitors bearing an oxadiazole ring in the scaffold. Our studies demonstrate that SLP120701, a SphK2-selective inhibitor (K-i = 1 mu M), decreases S1P levels in histiocytic lymphoma (U937) cells. Surprisingly, homologation with a single methylene unit between the oxadiazole and heterocyclic ring afforded a SphK1-selective inhibitor in SLP7111228 (K-i = 48 nM), which also decreased S1P levels in cultured U937 cells. In vivo application of both compounds, however, resulted in contrasting effect in circulating levels of S1P. Administration of SLP7111228 depressed blood S1P levels while SLP120701 increased levels of S1P. Taken together, these compounds provide an in vivo chemical toolkit to interrogate the effect of increasing or decreasing S1P levels and whether such a maneuver can have implications in disease states.
• A synthesis of the tetracyclic carboskeleton of isaindigotidione
  作者：Ch Yan Poon、Pauline Chiu

  DOI：10.1016/j.tetlet.2004.02.052

  日期：2004.3

  An efficient synthesis of the unique indolizino[7,6-c]quinoline carboskeleton of isaindigotidione has been achieved. This strategy employed L-proline and isatin as the main building blocks in the construction of the framework. Four transformations occurred in a one-pot operation to furnish the tetracyclic nucleus. (C) 2004 Elsevier Ltd. All rights reserved.