di-tert-butyl (2S)-5-hydroxypyrrolidine-1,2-dicarboxylate | 228579-90-6

• 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
• 英文名称: di-tert-butyl (2S)-5-hydroxypyrrolidine-1,2-dicarboxylate
• 英文别名: Di-tert-butyl (s)-5-hydroxypyrrolidine-1,2-dicarboxylate；ditert-butyl (2S)-5-hydroxypyrrolidine-1,2-dicarboxylate
• CAS: 228579-90-6
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: YFGRKTBRNCLLIA-RGURZIINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (2S)-5-hydroxypyrrolidine-1,2-dicarboxylate 生成 L-1-pyrroline-5-carboxylic acid
  参考文献：
  名称：

  In Vitro Reconstitution of the First Steps of Anatoxin-a Biosynthesis in Oscillatoria PCC 6506: From Free l-Proline to Acyl Carrier Protein Bound Dehydroproline

  摘要：

  Anatoxin-a and homoanatoxin-a are two potent cyanobacterial neurotoxins. We recently reported the identification of the gene cluster responsible for the biosynthesis of these toxins in cyanobacteria and proposed a biosynthetic scheme starting from L-proline and involving three polyketide synthases for which the starter would be (S)-1-pyrroline-5-carboxylate bound to an acyl carrier protein, AnaD. We now report the in vitro reconstitution of the first steps of this biosynthesis in Oscillatoria PCC 6506. We identified in PCC 6506 the gene coding for an Sfp-like phosphopantetheinyl transferase and purified the gene product, OsPPT, that catalyzed the transfer of the phosphopantetheinyl arm to the serine 41 of AnaD. The pure adenylation protein AnaC loaded L-proline oil holo-AnaD and was specific for L-proline (K-m = 0.97 mM, k(cat) = 68 min(-1)) among the 20 natural amino acids. Among six close structural analogues Of L-proline, including (S)-1-pyrroline-5-carboxylate, we only found 3,4-dehydro-L-proline to be ail alternate substrate for AnaC (K-m = 1.5 mM, k(cat) = 29 min(-1)). The putative prolyl-AnaD dehydrogenase, AnaB, purified to homogeneity as a histidine-tagged protein, showed an absorption Spectrum characteristic of FAD-containing proteins, it oxidized prolyl-AnaD to dehydroprolyl-AnaD as shown by tryptic digestion of the protein followed by liquid chromatography Coupled to tandem mass spectrometry. Alignment of the amino acid sequence of this dehydrogenase with related enzymes showed that AnaB belongs to the acyl-CoA dehydrogenase superfamily and thus probably catalyzes an alpha-beta-dehydrogenation of the thioester-bound proline followed by an aza-allylic isomerization to yield (S)-pyrroline-5-carboxyl-AnaD, the proposed starter for the Subsequent polyketide synthase, AnaE.

  DOI：

  10.1021/bi9018785
• 作为产物：
  描述：

  Boc-L-谷氨酸-1-叔丁酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 49.67h， 生成 di-tert-butyl (2S)-5-hydroxypyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  血管紧张素II类似物，包括5，9和5，10融合的硫杂双环烷三肽模拟物。

  摘要：

  已开发出一种简单的固相实验程序，用于构建采用β-转角的新的三肽5，9和5，10融合的硫杂双环烷烃骨架。这种N端定向双环化反应依赖于谷氨酸衍生的掩盖醛前体作为关键构件，为之前报道的相关双环化反应提供了补充，在这种情况下，天冬氨酸衍生的前体被用来诱导向C端环化。肽。因此，可以简单地通过改变掺入的醛前体的链长来改变双环化的区域选择性。合成了高血压八肽血管紧张素II的四个类似物，包括在3-5-和5-7位置的新支架。这些构象约束的血管紧张素II类似物之一表现出AT（1）受体亲和力（K（i）= 750 nM）。提出了从理论构象分析的双环三肽模拟物的模型化合物的结果，它们表明几何形状的细微差别对与AT（1）受体的亲和力有很大影响。

  DOI：

  10.1021/jm991089q

文献信息

• INDUCTION OF ALPHA HELIX CONFORMATIONS IN PROTEINS AND PEPTIDES
  申请人：Schmalz Hans-Günther

  公开号：US20120172402A1

  公开（公告）日：2012-07-05

  Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.

  公式（I）中的替代三环二脯氨酸类似物，其中变量如本文所定义。还披露了其生产方法，用于诱导肽和/或蛋白质呈α-螺旋构象的用途，含有该化合物的药物，含有该化合物的肽库的生产方法，以及含有该化合物的肽库。
• STRUCTURAL MIMETICS OF PROLINE-RICH PEPTIDES AND THE PHARMACEUTICAL USE THEREOF
  申请人：Kuehne Ronald

  公开号：US20110034438A1

  公开（公告）日：2011-02-10

  The invention relates to compounds of general formula (I), which can be used particularly as structural mimetics of proline-rich peptides and are therefore capable of binding PRM binding domains (proline-rich motif binding domains) of proteins. The invention also relates to the use of said compounds as pharmaceutical active agents and the use of these pharmaceutical active agents for treating bacterial diseases, neurodegenerative diseases and tumours.

  该发明涉及一般式（I）的化合物，可用作脯氨酸富集肽的结构模拟体，因此能够结合蛋白质的PRM结合结构域（脯氨酸富集基序结合结构域）。该发明还涉及将这些化合物用作药用活性剂，并将这些药用活性剂用于治疗细菌性疾病、神经退行性疾病和肿瘤。
• Addressing Protein-Protein Interactions with Small Molecules: A Pro-Pro Dipeptide Mimic with a PPII Helix Conformation as a Module for the Synthesis of PRD-Binding Ligands
  作者：Jan Zaminer、Christoph Brockmann、Peter Huy、Robert Opitz、Cédric Reuter、Michael Beyermann、Christian Freund、Matthias Müller、Hartmut Oschkinat、Ronald Kühne、Hans-Günther Schmalz

  DOI：10.1002/anie.201001739

  日期：2010.9.17

  be incorporated, without loss of binding ability, as a Pro‐Pro substitute into two peptides that bind to the proline‐rich motif‐recognizing domains Fyn‐SH3. The dipeptide analogue X, which is locked in a polyproline type II helix conformation, is created by stereoselective introduction of a vinylidene bridge into a diproline unit.

  X标记斑点：可以将合成的三环氨基酸X（见结构； C灰色，H青色，N蓝色，O红色，双键黄色）并入Pro-Pro替代品中，而不会失去结合能力，成为两个肽与富含脯氨酸的基序识别结构域Fyn-SH3结合。通过将亚乙烯基桥立体选择性地引入到双脯氨酸单元中，可以生成被锁定在II型多脯氨酸螺旋构象中的二肽类似物X。
• Insights into the Reaction Mechanism of the Prolyl–Acyl Carrier Protein Oxidase Involved in Anatoxin-a and Homoanatoxin-a Biosynthesis
  作者：Stéphane Mann、Bérangère Lombard、Damarys Loew、Annick Méjean、Olivier Ploux

  DOI：10.1021/bi200892a

  日期：2011.8.23

  for the biosynthesis of these toxins as well as the in-vitro reconstitution of the first steps of this biosynthesis. We now report experimental evidence supporting the proposed reaction mechanism of AnaB, a flavoprotein homologous to acyl-CoA dehydrogenase. AnaB catalyzes the two-electron oxidation of prolyl-AnaD, which is proline linked to the acyl carrier protein holo-AnaD, to dehydroprolyl-AnaD

  Anatoxin-a和homoanatoxin-a是两种有效的蓝细菌神经毒素。我们最近报道了负责这些毒素的生物合成以及该生物合成第一步的体外重建的基因簇的鉴定。我们现在报告支持AnaB（一种与酰基辅酶A脱氢酶同源的黄素蛋白）的拟议反应机制的实验证据。AnaB催化脯氨酸与酰基载体蛋白holo-AnaD连接的脯氨酸的双电子氧化，以氧气为第二种底物，将脯氨酰-AnaD氧化为脱氢脯氨酰-AnaD。因此，AnaB是一种氧化酶。通过使用液相色谱与串联质谱联用（LC-MS / MS），我们已经鉴定并表征了AnaB产品脱氢脯氨酰-AnaD。我们估计了1 min –1的表观催化常数。用于AnaB催化。我们合成了几种氘标记的脯氨酸，并通过酶法将其转化为相应的脯氨酰-AnaD。这些氘标记的脯氨酰AnaD在AnaB存在下被氧化，并通过LC-MS / MS测定剩余底物中和产物中的氘标记。数据支持了一种反应机理，该机
• [DE] NEUE CYANOPYRROLIDIDE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS ARZNEIMITTEL<br/>[EN] NOVEL CYANOPYRROLIDIDES, METHODS FOR THE PRODUCTION THEREOF, AND USE OF THE SAME AS MEDICAMENTS<br/>[FR] NOUVEAUX CYANOPYRROLIDIDES, PROCEDES POUR LEUR PRODUCTION ET LEUR UTILISATION COMME MEDICAMENT
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2005012308A1

  公开（公告）日：2005-02-10

  Die Erfindung betrifft Verbindungen der Formel (I), worin die Reste die im Text angegebenen Bedeutungen haben, deren stereoisomeren Formen sowie deren physiologisch verträglichen Salze, physiologisch funktionellen Derivate und Verfahren zu deren Herstellung. Die Verbindungen eignen sich zur Behandlung von Erkrankungen des Stoffwechsels, wie des Typ 2 Diabetes.

  该发明涉及公式（I）的化合物，其中残基具有文本中指定的含义，它们的立体异构体形式以及其生理相容盐，生理功能衍生物和制备方法。这些化合物适用于治疗代谢疾病，如2型糖尿病。