(2R,4R,5S)-2-((S)-aziridin-2-yl)-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (2R,4R,5S)-2-((S)-aziridin-2-yl)-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol
• 英文别名: (S)-aziridine-2-carboxaldehyde dimer；(2R,4R,5S)-2-[(2S)-aziridin-2-yl]-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol
• 化学式: C₆H₁₀N₂O₂
• 分子量: 142.158
• InChiKey: WLKQLTSLRNRVSR-PHNLHORASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异氰酸叔丁酯 、 (2R,4R,5S)-2-((S)-aziridin-2-yl)-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol 、 L-哌啶-2-甲酸 以 2,2,2-三氟乙醇 为溶剂， 反应 22.0h， 以71%的产率得到(3aS,9S,9aS)-N-tert-butyl-3-oxooctahydro-1H-azirino[1,2-a]pyrido[1,2-d]pyrazine-9-carboxamide
  参考文献：
  名称：

  Stereocontrolled Disruption of the Ugi Reaction toward the Production of Chiral Piperazinones: Substrate Scope and Process Development

  摘要：

  The factors determining diastereoselectivity observed in the multicomponent conversion of amino acids, aziridine aldehyde dimers, and isocyanides into chiral piperazinones have been investigated. Amino acid-dependent selectivity for either trans- or cis-substituted piperazinone products has been achieved. An experimentally determined diastereoselectivity model for the three-component reaction driven by aziridine aldehyde dimers has predictive value for different substrate classes. Moreover, this model is useful in reconciling the previously reported observations in multicomponent reactions between isocyanides, alpha-amino acids, and monofunctional aldehydes.

  DOI：

  10.1021/jo5018316
• 作为产物：
  描述：

  methyl aziridine-2-carboxylate 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 5.5h， 以76%的产率得到(2R,4R,5S)-2-((S)-aziridin-2-yl)-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol
  参考文献：
  名称：

  WO2008/46232

  摘要：

  公开号：

文献信息

• Thioester-isocyanides: versatile reagents for the synthesis of cycle–tail peptides
  作者：Benjamin H. Rotstein、David J. Winternheimer、Lois M. Yin、Charles M. Deber、Andrei K. Yudin

  DOI：10.1039/c2cc16027g

  日期：——

  A novel class of reagents, thioester isocyanides, have been prepared and applied in the synthesis of peptide macrocycles. The isocyanide part of the molecule is deployed in a multicomponent macrocyclization step. This step is followed by chemoselective peptide ligation at the thioester part of the macrocycle. Our method can now be used for rapid assembly and evaluation of cycle–tail peptides.

  一种新型试剂，硫酯异氰酸酯，已经被合成并应用于肽大环的合成。分子的异氰酸酯部分在多组分大环化步骤中被使用。此步骤之后是对大环的硫酯部分进行化学选择性肽连接。我们的方法现在可以用于快速组装和评估环-尾肽。
• Solid-Phase Parallel Synthesis of Functionalised Medium-to-Large Cyclic Peptidomimetics through Three-Component Coupling Driven by Aziridine Aldehyde Dimers
  作者：Adam P. Treder、Jennifer L. Hickey、Marie-Claude J. Tremblay、Serge Zaretsky、Conor C. G. Scully、John Mancuso、Annie Doucet、Andrei K. Yudin、Eric Marsault

  DOI：10.1002/chem.201500068

  日期：2015.6.15

  solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.

  描述了使用氮丙啶醛二聚体驱动的三组分偶联的大环肽的首次固相平行合成。该方法支持合成9至18元含氮丙啶的大环，然后通过氮丙啶环的亲核开环将其官能化。这构成了快速并行合成大环肽的可靠方法。
• Synthesis of Chiral Piperazinones Using Amphoteric Aziridine Aldehyde Dimers and Functionalized Isocyanides
  作者：Niklas B. Heine、Sherif J. Kaldas、Lee Belding、Olga Shmatova、Travis Dudding、Valentine G. Nenajdenko、Armido Studer、Andrei K. Yudin

  DOI：10.1021/acs.joc.6b00471

  日期：2016.6.17

  functionalized isocyanides in the aziridine aldehyde-driven multicomponent synthesis of piperazinones. High diasteroselectivity for each isocyanide was observed. A theoretical evaluation of the reaction course corroborates the experimental data. Moreover, the reactivity of cis- and trans-configured aziridine aldehyde dimers has been compared. This study further probes the dimer-driven mechanism of

  我们在哌嗪酮的氮丙啶醛驱动的多组分合成中评估了一系列官能化的异氰化物。观察到每种异氰酸酯的高非对映选择性。反应过程的理论评估证实了实验数据。此外，已经比较了顺式和反式氮丙啶醛二聚体的反应性。这项研究进一步探讨了二聚体驱动环化的机制，并能够有效地获得各种带有功能化侧链的手性哌嗪酮。
• Bicycle synthesis through peptide macrocyclization using aziridine aldehydes followed by late stage disulfide bond installation
  作者：Benjamin K. W. Chung、Jennifer L. Hickey、Conor C. G. Scully、Serge Zaretsky、Andrei K. Yudin

  DOI：10.1039/c3md00054k

  日期：——

  We present a method that can be applied to generate medium-sized peptidomimetic macrocycles equipped with disulfide bonds.

  我们提出了一种方法，可以用于生成配备二硫键的中等大小肽类模拟环。
• Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics
  作者：Kristin E. Low、Spencer Ler、Kevin J. Chen、Robert L. Campbell、Jennifer L. Hickey、Joanne Tan、Conor C. G. Scully、Peter L. Davies、Andrei K. Yudin、Serge Zaretsky

  DOI：10.1021/acs.jmedchem.6b00267

  日期：2016.6.9

  Our previously reported structures of calpain bound to its endogenous inhibitor calpastatin have motivated the use of aziridine aldehyde-mediated peptide macrocyclization toward the design of cyclic peptides and peptidomimetics as calpain inhibitors. Inspired by nature’s hint that a β-turn loop within calpastatin forms a broad interaction around calpain’s active site cysteine, we have constructed and

  我们以前报道的钙蛋白酶与它的内源性抑制剂钙蛋白酶抑制素的结构，已经促使使用氮丙啶醛介导的肽大环化来设计环肽和拟肽作为钙蛋白酶抑制剂。受自然界的提示启发，钙调他汀内的一个β-turn环在钙蛋白酶的活性位点半胱氨酸周围形成了广泛的相互作用，我们基于该环序列构建并测试了45种肽类化合物的文库。四个分子显示出对calpain-2的可抑制性低的微摩尔抑制。进一步的系统序列变化导致了探针的发展，该探针显示出比其他半胱氨酸蛋白酶更高的针对钙蛋白酶的抑制力和特异性。计算的K i该值在低微摩尔范围内，可与其他拟肽钙蛋白酶抑制剂相抗衡，并且对其他与治疗相关的蛋白酶具有更高的选择性。观察到了针对钙蛋白酶2的竞争性和混合抑制作用，并且在酶上的变构抑制位点被确定为非竞争性抑制剂。