(S)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide

• 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: (S)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide
• 英文别名: (S)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide；N-(pyridin-3-yl)pyrrolidine-2-carboxamide；(2S)-N-pyridin-3-ylpyrrolidine-2-carboxamide
• 化学式: C₁₀H₁₃N₃O
• 分子量: 191.233
• InChiKey: HOQVOMSGUVLPIL-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide 在 一水合肼 、 甲基磺酰氯 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 22.5h， 生成 (S)-1-(2-benzoylhydrazine-1-carbonyl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  作为具有抗乳腺癌活性的选择性 CDK4/6 抑制剂的 N-(pyridin-3-yl) 脯氨酸新骨架的合成和鉴定

  摘要：

  CDK4/6是治疗恶性肿瘤的有吸引力的化疗靶点，CDK4/6选择性抑制剂在乳腺癌治疗中做出了突出贡献。然而，这些抑制剂具有单一的N- (pyridin-2-yl) pyrimidin-2-amine骨架，无法克服临床应用中的副作用。在我们之前的研究中，通过分析 CDK6 的活性位点特征，将一个N'-乙酰基吡咯烷-1-碳酰肼作为初始片段命中。通过片段生长法获得了两个系列的N- (pyridin-3-yl)脯氨酸。根据针对 CDK4/6 和两种化合物7c和7p的体外活性数据进行 QSAR 研究发现具有有效抑制活性的CDK4以不同的结合构象与CDK4相互作用。它们显示出对乳腺癌细胞增殖的潜在抑制作用，并且7c在体内表现出有希望的抗乳腺癌作用。

  DOI：

  10.1016/j.bioorg.2021.105547
• 作为产物：
  描述：

  N-苄氧羰基-L-脯氨酸 在 palladium on activated charcoal 氢气 、 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 (S)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide
  参考文献：
  名称：

  Design of Highly Enantioselective Organocatalysts Based on Molecular Recognition

  摘要：

  Various organocatalysts have been designed based on molecular recognition to catalyze the asymmetric direct aldol reaction of ketones with aryl and alkyl alpha-keto acids, affording beta-hydroxyl carboxylic acids with a tertiary stereogenic center with excellent enantioselectivities of up to 98% ee. A linear effect was observed for the reaction, demonstrating a single molecule of the catalyst involved in the catalysis.

  DOI：

  10.1021/ol0529391
• 作为试剂：
  描述：

  1-苄基-1H-吲哚-2,3-二酮 、 丙酮 在 (S)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide 作用下， 以 水 为溶剂， 反应 44.0h， 生成 (R)-1-benzyl-3-hydroxy-3-(2'-oxopropyl)indolin-2-one 、 (S)-1-benzyl-3-hydroxy-3-(2-oxopropyl)indolin-2-one
  参考文献：
  名称：

  Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective aldol reaction of acetone with isatin

  摘要：

  We have screened a range of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts incorporating N-pyridyl and N-quinolinyl groups in the synthetically useful aldol reaction of isatin with acetone. The 'reverse amide' N-pyridyl pyrrolidinylmethyl amide catalysts proved highly catalytically active but gave disappointing enantioselectivities. However, an N-3-pyridyl prolinamide catalyst gave the aldol adduct in high yields and high enantioselectivity with up to 72% ee of the (S)-isomer. Conditions were optimised for this catalyst and in particular an additive screen identified a link between the pK(a) of the acid additive and the yield and enantioselectivity. An N-arylsulfonamide prolinamide was also identified as a catalyst for this reaction giving the (R)-enantiomer in 68% ee. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.07.016

文献信息

• Asymmetric Organocatalytic Direct Aldol Reactions of Ketones with α-Keto Acids and Their Application to the Synthesis of 2-Hydroxy-γ-butyrolactones
  作者：Xiao-Ying Xu、Zhuo Tang、Yan-Zhao Wang、Shi-Wei Luo、Lin-Feng Cun、Liu-Zhu Gong

  DOI：10.1021/jo701868t

  日期：2007.12.1

  of organocatalysts for the asymmetric direct aldol reactions of ketones with α-keto acids were designed on the basis of molecular recognition and prepared from proline and aminopyridines. The organic molecule 8e, derived from proline and 6-methyl-2-amino pyridine, was the best catalyst, affording excellent enantioselectivities (up to 98% ee) for the direct aldol reactions of acetone or 2-butanone with

  在分子识别的基础上，设计了多种有机催化剂，用于酮与α-酮酸的不对称直接羟醛直接反应，并由脯氨酸和氨基吡啶制备。有机分子8e衍生自脯氨酸和6-甲基-2-氨基吡啶的最佳催化剂，对丙酮或2-丁酮与各种α-酮酸和用于各种无环脂族酮与3-（2-硝基苯基）-2-氧代丙酸的反应。通过非对映选择性还原和内酯化的反应序列可以将羟醛加成物转化为2-羟基-γ-丁内酯。对过渡态的实验和理论研究表明，有机催化剂的酰胺N和吡啶N分别与α-酮酸的酮氧基和羧酸羟基选择性地形成氢键。这两个氢键相互作用对于直接不对称羟醛缩合的反应性和对映选择性很重要。
• Facile evolution of asymmetric organocatalysts in water assisted by surfactant Brønsted acids
  作者：Sanzhong Luo、Hui Xu、Jiuyuan Li、Long Zhang、Xueling Mi、Xiaoxi Zheng、Jin-Pei Cheng

  DOI：10.1016/j.tet.2007.08.096

  日期：2007.11

  benzenesulfonic acid (DBSA) leads to highly effective and selective organocatalysts in water. The in situ generated catalysts catalyze highly stereoselective desymmetrization of prochiral ketones via direct aldol reactions (up to >16:1 dr, >99% ee) in water using micelle as reaction media. The current strategy was also applied in asymmetric Michael addition leading to a catalytic system with good activity

  手性胺和表面活性剂布朗斯台德酸（例如对十二烷基苯磺酸（DBSA））的简单混合可在水中产生高效和选择性的有机催化剂。原位生成的催化剂使用胶束作为反应介质，通过在水中的直接羟醛反应（高达> 16：1 dr，> 99％ee）催化前手性酮的高度立体选择性去对称化。当前的策略还用于不对称迈克尔加成中，从而产生具有良好活性和立体选择性的催化体系。
• Dynamic assembly of a zinc-templated bifunctional organocatalyst in the presence of water for the asymmetric aldol reaction
  作者：Anna Serra-Pont、Ignacio Alfonso、Ciril Jimeno、Jordi Solà

  DOI：10.1039/c5cc07847d

  日期：——

  A bifunctional organocatalytic system consisting of simple pyridine ligands containing the separate catalytic functionalities was assembled using ZnCl2. This novel metal-templated catalyst furnished high yields and stereoselectivities towards the aldol...

  使用ZnCl2组装了一个双官能有机催化体系，该体系由简单的吡啶配体组成，该吡啶配体包含单独的催化官能团。这种新型的金属模板催化剂对醛醇缩合物提供了高收率和立体选择性。
• A copper-templated, bifunctional organocatalyst: a strongly cooperative dynamic system for the aldol reaction
  作者：Anna Serra-Pont、Ignacio Alfonso、Jordi Solà、Ciril Jimeno

  DOI：10.1039/c7ob01370a

  日期：——

  A copper-templated bifunctional organocatalyst delivers aldol adducts in high yields and stereoselectivities.

  一个以铜为模板的双功能有机催化剂以高产率和立体选择性提供醛醇加合物。
• Porous Peptide Complexes by a Folding-and-Assembly Strategy
  作者：Tomohisa Sawada、Motoya Yamagami、Shuji Akinaga、Tatsuki Miyaji、Makoto Fujita

  DOI：10.1002/asia.201700458

  日期：2017.7.18

  new porous peptide structure through a coordination-driven folding-and-assembly strategy. A porous framework with 1.5 nm-sized pores and a PII helical peptide scaffold was successfully obtained by complexation of AgNTf2 and tripeptide ligands containing the Gly-Pro-Pro sequence. The pores were modified in various ways with retention of the latent PII helical conformation of the peptide ligand.

  一致的折叠和组装过程对于蛋白质自组装是必需的，但是合成化学家很少尝试这种一致的策略。在这项工作中，我们通过协调驱动的折叠和组装策略创建了一种新的多孔肽结构。通过将AgNTf 2与包含Gly-Pro-Pro序列的三肽配体复合，成功获得了具有1.5 nm大小的孔和P II螺旋肽支架的多孔骨架。用保留肽配体的潜在P II螺旋构象以各种方式修饰孔。