(R)-1-叔丁基2-甲基-2-烯丙基吡咯烷-1,2-二羧酸酯 | 112348-45-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (R)-1-叔丁基2-甲基-2-烯丙基吡咯烷-1,2-二羧酸酯
• 英文名称: (R)-N-(tert-butoxycarbonyl)-2-allylproline methyl ester
• 英文别名: 1-(tert-Butyl) 2-methyl (R)-2-allylpyrrolidine-1,2-dicarboxylate；1-O-tert-butyl 2-O-methyl (2R)-2-prop-2-enylpyrrolidine-1,2-dicarboxylate
• CAS: 112348-45-5
• 化学式: C₁₄H₂₃NO₄
• 分子量: 269.341
• InChiKey: VEYTWFFJGOYPRZ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-叔丁基2-甲基-2-烯丙基吡咯烷-1,2-二羧酸酯 在 sodium hydroxide 、 sodium periodate 、 四氧化锇 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.5h， 生成 <3'-(S)-<3'α,6'α(R*),7'aα>>-1-(tert-butoxycarbonyl)tetrahydro-5'-oxospirothiazolidine>-3'-N-methylcarboxamide
  参考文献：
  名称：

  Genin, Michael J.; Johnson, Rodney L., Journal of the American Chemical Society, 1992, vol. 114, # 23, p. 8778 - 8783

  摘要：

  DOI：
• 作为产物：
  描述：

  (3R,7aR)-7a-allyl-3-(trichloromethyl)tetrahydropyrrolo[1,2-c]oxazol-1(3H)-one 在 4-二甲氨基吡啶 、 sodium 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (R)-1-叔丁基2-甲基-2-烯丙基吡咯烷-1,2-二羧酸酯
  参考文献：
  名称：

  对映体纯链，环状和氟化α-氨基酸的收敛合成

  摘要：

  描述了自由基保护的多种受保护的对映纯α-氨基酸（包括氟化衍生物）的合成。自由基的加成提供了天然潜伏的巯基-α-氨基酸，非常适合天然化学连接。

  DOI：

  10.1021/acs.orglett.6b00656

文献信息

• A Highly Practical RCM Approach towards a Molecular Building Kit of Spirocyclic Reverse Turn Mimics
  作者：Holger Bittermann、Frank Böckler、Jürgen Einsiedel、Peter Gmeiner

  DOI：10.1002/chem.200600432

  日期：2006.8.16

  privileged molecular scaffolds efficiently mimicking reverse turn motifs and thus increasing both binding and selectivity and enabling the elucidation of the bioactive conformation of a natural peptide has attracted remarkable interest. The frequent occurrence of proline in various turn patterns initiated the design of proline-based reverse turn mimetics. As a structural hybridization of a highly potent

  特权分子支架的开发有效地模仿了反向转位基序，从而增加了结合和选择性，并使得能够阐明天然肽的生物活性构象引起了人们的极大兴趣。脯氨酸在各种转弯模式中的频繁出现启动了基于脯氨酸的反向转弯模拟物的设计。作为高效模拟VI型IIβ转角的高效VI型β转角诱导物1与饱和螺环内酰胺3的结构杂交，当Seebach的手性方法的自我复制获得成功时，我们开发了一条通向2型不饱和螺环内酰胺的通用合成路线。与肽偶联反应和Grubbs的闭环复分解反应相结合。通过这种方式，遵循统一的途径，可以获得具有六至九元内酰胺环的各种模型肽。将适当保护的模板引入固相肽合成中会产生天然存在的神经肽神经降压素的不饱和螺环类似物。在高水平的理论上进行的光谱研究和DFT计算表明，反向旋转诱导能力对环尺寸的显着依赖性。尽管不饱和螺环ε-内酰胺12的二级结构与参考γ-内酰胺3a非常吻合，但不饱和δ-内酰胺11却具有超强的β-转角诱导作用，甚至优于3b型β-内酰胺。
• Evaluation of Lactam-Bridged Neurotensin Analogues Adjusting ψ(Pro¹⁰) Close to the Experimentally Derived Bioactive Conformation of NT(8−13)
  作者：Holger Bittermann、Jürgen Einsiedel、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm049644y

  日期：2004.10.1

  The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a beta-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies showed that the restriction of Psi(Pro(10)) to approximately 130degrees leads to a more than 1000-fold increase of binding affinity for 1 (K-i = 12 nM) when compared to the more flexible analogue [NMeTyr(11)]NT(8-13).
• Spirolactams as Conformationally Restricted Pseudopeptides:  Synthesis and Conformational Analysis
  作者：M. Montserrat Fernández、Anna Diez、Mario Rubiralta、Elvira Montenegro、Núria Casamitjana、Marcelo J. Kogan、Ernest Giralt

  DOI：10.1021/jo025999i

  日期：2002.11.1

  The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-Gly-Leu}-Met-NH2 derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.
• Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88
  作者：Nicola Fantò、Grazia Gallo、Andrea Ciacci、Mauro Semproni、Davide Vignola、Marco Quaglia、Valentina Bombardi、Domenico Mastroianni、M. Pia Zibella、Giancarlo Basile、Marica Sassano、Vito Ruggiero、Rita De Santis、Paolo Carminati

  DOI：10.1021/jm070723u

  日期：2008.3.13

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.
• Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain
  作者：Matthew C. Lucas、Robert J. Weikert、David S. Carter、Hai-Ying Cai、Robert Greenhouse、Pravin S. Iyer、Clara J. Lin、Eun Kyung Lee、Ann Marie Madera、Amy Moore、Kerem Ozboya、Ryan C. Schoenfeld、Sandra Steiner、Yansheng Zhai、Stephen M. Lynch

  DOI：10.1016/j.bmcl.2010.07.020

  日期：2010.9

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.