tert-butyl (S)-2-(hydroxycarbamoyl)pyrrolidine-1-carboxylate | 96792-04-0

• 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: tert-butyl (S)-2-(hydroxycarbamoyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-(hydroxycarbamoyl)pyrrolidine-1-carboxylate
• CAS: 96792-04-0
• 化学式: C₁₀H₁₈N₂O₄
• 分子量: 230.264
• InChiKey: QRXFGAFSGGJJHI-ZETCQYMHSA-N

物化性质

• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-(hydroxycarbamoyl)pyrrolidine-1-carboxylate 在 盐酸 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 90.0h， 生成 (S)-2-(5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl)pyrrolidine-1-carboximidamide hydrochloride
  参考文献：
  名称：

  Structure−Activity Relationship Studies and in Vivo Activity of Guanidine-Based Sphingosine Kinase Inhibitors: Discovery of SphK1- and SphK2-Selective Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm501760d
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 吡啶 、 盐酸羟胺 作用下， 以100%的产率得到tert-butyl (S)-2-(hydroxycarbamoyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers

  摘要：

  Design and synthesis of pyrazolodihydropyrimidines as K(V)1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.085

文献信息

• An Environmentally Sustainable Mechanochemical Route to Hydroxamic Acid Derivatives
  作者：Rita Mocci、Lidia De Luca、Francesco Delogu、Andrea Porcheddu

  DOI：10.1002/adsc.201600350

  日期：2016.10.6

  An operationally simple, and cost efficient conversion of carboxylic acids into hydroxamic acid derivatives via a high‐energy mechanochemical activation is presented. This ball milling methodology was applied to a wide variety of carboxylic acids dramatically improving purification issues associated with this class of molecules, which still remain one of the main bottlenecks of classical methodologies

  提出了通过高能机械化学活化将羧酸简单，经济地转化为异羟肟酸衍生物的方法。该球磨方法论已应用于多种羧酸，大大改善了与此类分子相关的纯化问题，而这些问题仍然是经典方法学的主要瓶颈之一。
• Simple One-Flask Method for the Preparation of Hydroxamic Acids
  作者：Giampaolo Giacomelli、Andrea Porcheddu、Margherita Salaris

  DOI：10.1021/ol034903j

  日期：2003.7.1

  [reaction: see text] A one-step conversion of carboxylic acids to hydroxamic acids under very mild conditions is described. This simple and efficient method has been applied for the synthesis of enantiopure hydroxamate of alpha-amino acids and peptides.

  [反应：见正文]描述了在非常温和的条件下将羧酸一步转化为异羟肟酸的方法。这种简单而有效的方法已被用于合成α-氨基酸和肽的对映体纯异羟肟酸酯。
• Organocatalytic Multicomponent Synthesis of α/β‐Dipeptide Derivatives
  作者：Thomas Martzel、Julien Annibaletto、Pierre Millet、Etienne Pair、Morgane Sanselme、Sylvain Oudeyer、Vincent Levacher、Jean‐François Brière

  DOI：10.1002/chem.202001214

  日期：2020.7.14

  multicomponent Knoevenagel‐aza‐Michael‐cyclocondensation reaction involving readily available hydroxamic acid‐derived from naturally occurring α‐amino acids allows a diversity‐oriented synthesis of novel isoxazolidin‐5‐ones possessing an N‐protected α‐amino acid pendant with good to high diastereoselectivities thanks to a match effect with a chiral organocatalyst. These diversely substituted heterocycles

  简单的多组分Knoevenagel-氮杂-Michael-环缩合反应涉及容易得的天然存在的α-氨基酸衍生的异羟肟酸，可实现具有N-保护的α-氨基酸侧基且具有良好保护作用的新型异恶唑烷5-5异构体的合成。与手性有机催化剂的匹配作用，使非对映选择性高。这些被不同取代的杂环很容易作为单个非对映异构体分离，被证明是形成一系列α/β-二肽片段的通用平台。
• AsymmetricDiels-Alder Cycloadditions with Chiral Carbamoyl Dienophiles
  作者：Albert Defoin、Agn�s Brouillard-Poichet、Jacques Streith

  DOI：10.1002/hlca.19920750108

  日期：1992.2.5

  Chiral acylnitroso dienophiles 14, which were obtained from L-proline and from D-mandelic acid, reacted with cyclohexa-1,3-diene to give the expected diastereoisomers 15 and 16 (Scheme 2 and Table 1). The d.e. values for these Diels-Alder reactions were moderate; they are related to the molecular stiffness of the dienophiles. The absolute configuration of the major cycloadducts was interpreted in terms

  由L-脯氨酸和D-扁桃酸获得的手性酰基亚硝基二亲烯体14与环己-1,3-二烯反应，得到预期的非对映异构体15和16（方案2和表1）。这些Diels - Alder反应的de值中等。它们与亲二烯体的分子刚度有关。主要的环加合物的绝对构型是根据HOMO / LUMO相互作用来解释的，方法是“内”，而acylintroso二烯亲和体则从其顺式构象反应。
• 一种(1R ,3S)-3-氨基环戊醇盐酸盐的制备方法
  申请人：广东莱佛士制药技术有限公司

  公开号：CN109651178A

  公开（公告）日：2019-04-19

  本发明公开了一种(1R,3S)‑3‑氨基环戊醇盐酸盐的制备方法，该方法以手性羧酸与羟胺形成的酰胺作为手性源，在铜催化的氧化反应体系中快速得到手性的狄尔斯‑阿尔德反应产物，之后经过还原反应和碱性脱保护反应，以及酸化反应后得到目标产物。手性诱导试剂手性羧酸经简单酸化、萃取处理可回收再利用。这种(1R,3S)‑3‑氨基环戊醇盐酸盐的制备方法具有较高的操作安全性及较高的选择性，原料易得，成本较低，反应时间短和工艺流程简单等优点。