(2S)-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]pyrrolidine-2-carboxamide

• 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: (2S)-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]pyrrolidine-2-carboxamide
• 英文别名: (S)-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]pyrrolidine-1-carboxamide；(S)-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]pyrrolidine-2-carboxamide；(S)-N-((1S,2R)-2-hydroxy-1-indanyl)pyrrolidine-5-carboxamide；(2S)-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]pyrrolidine-2-carboxamide
• 化学式: C₁₄H₁₈N₂O₂
• 分子量: 246.309
• InChiKey: NEZIIRPIEDUFFK-XQQFMLRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenethyloxirane-2-carboxylic acid 、 (2S)-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]pyrrolidine-2-carboxamide 在 N,N-二异丙基乙胺 、 ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到(5S)-N-((1S,2R)-2-hydroxy-1-indanyl)-1-(2-phenethyloxirane-2-carbonyl)pyrrolidine-5-carboxamide
  参考文献：
  名称：

  α-取代的去甲他汀作为多种消化液空泡疟疾天冬氨酸蛋白酶抑制剂的过渡态模拟物

  摘要：

  研究了含降nor素的纤溶酶抑制剂中P1侧链从β位置移动到α位置的影响，产生了两类新的含叔醇的α-苄基去甲他汀和α-苯基去甲他汀。设计，合成和评估了十二种α-取代的诺他汀类药物对所有四种导致人类疟疾的疟原虫的消化液中存在的纤溶酶II和纤溶酶IV直向同源物（PM4）的抑制作用。已开发出新的合成路线来生产所需的α-取代的诺他汀类药物，为纯立体异构体。最好的化合物为所有PM4提供的K i值都在纳摩尔范围内，椭圆疟原虫的PM4的最佳值为110 nM。另外，获得了与密切相关的人天冬氨酸蛋白酶组织蛋白酶D的优异的选择性。通过使用线性相互作用能法（LIE）计算抑制剂与蛋白质的结合亲和力，可以合理化丧失P1取代基后对恶性疟原虫PM4的亲和力。

  DOI：

  10.1016/j.bmc.2009.06.065
• 作为产物：
  描述：

  (S)-benzyl 2-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-ylcarbamoyl]pyrrolidine-1-carboxylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以85%的产率得到(2S)-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  通过 1,2-氨基醇衍生的脯氨酰胺作为双功能催化剂，酮与 β-硝基苯乙烯的不对称共轭加成

  摘要：

  这项工作得到了教育部长和 Ciencia 的 Direccion General de Investigacion (CTQ2004-00808/BQU)、Generalitat Valenciana (CTIOIB/2002/320、GRUPOS03/134、GRUPOS05/11 和 GV05) 和 GV05/阿利坎特大学。

  DOI：

  10.1002/ejoc.200700031
• 作为试剂：
  描述：

  1-nitro-2-(4-chlorophenyl)ethylene 、 3-戊酮 在 (2S)-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]pyrrolidine-2-carboxamide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 96.0h， 生成 5-(4-chlorophenyl)-4-methyl-6-nitrohexan-3-one 、 、 5-(4-chlorophenyl)-4-methyl-6-nitrohexan-3-one
  参考文献：
  名称：

  Enantioselective conjugate addition of ketones to β-nitrostyrenes catalyzed by 1,2-amino alcohol-derived prolinamides

  摘要：

  Various L-prolinamides 14, prepared from L-proline and chiral beta-amino alcohols, are active bifunctional catalysts for the direct nitro-Michael addition of ketones to beta-nitrostyrenes. In particular, catalyst 14e prepared from L-proline and (1S,2R)-cis-1amino-2-indanol exhibits the highest catalytic performance working in polar aprotic solvents such as NMP. High syn-diastereoselectivities (up to 94% de) and good enantioselectivities (up to 80% ee) were obtained at rt. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2006.07.023

文献信息

• Evaluation of Ligands for Ketone Reduction by Asymmetric Hydride Transfer in Water by Multi‐Substrate Screening
  作者：Saoussen Zeror、Jacqueline Collin、Jean‐Claude Fiaud、Louisa Aribi Zouioueche

  DOI：10.1002/adsc.200700272

  日期：2008.1.4

  Various ligands for the ruthenium-catalyzed enantioselective reduction of ketones in water have been investigated. Multi-substrate reactions have been carried out for the comparison of various proline amides and aminoalcohol ligands. Two sets of six aromatic ketones have been selected in order to evaluate the enantiomeric excesses of all the resulting alcohols by a single chromatographic analysis.

  已经研究了用于钌催化的水中酮对映选择性还原的各种配体。为了比较各种脯氨酸酰胺和氨基醇配体，已经进行了多底物反应。为了通过单次色谱分析评估所有所得醇的对映体过量，已选择了两组六种芳族酮。由（1 R，2 S）-顺式制备的脯氨酸酰胺衍生物-氨基茚满醇显示为多底物还原反应中使用的大多数酮的最佳配体。该配体已用于多种其他芳香族酮的对映选择性还原，并且在所有情况下，与我们以前的工作中使用的苯脯氨酰胺相比，对映体过量都得到了改善。
• Synthesis of a New Proline‐Derived Organic Catalyst and Its Evaluation for Direct Aldol Reaction
  作者：Shinji Tanimori、Toshihito Naka、Mitsunori Kirihata

  DOI：10.1081/scc-200036576

  日期：2004.12.31

  Abstract Aldol condensation of isobutylaldehyde with acetone catalyzed by amides and amines (1–8) derived from L‐proline gave β‐hydroxy ketone 17 in 80%ee.

  摘要 在衍生自 L-脯氨酸的酰胺和胺 (1-8) 的催化下，异丁醛与丙酮的羟醛缩合得到 80%ee 的 β-羟基酮 17。
• Prolinamides<i>versus</i>Prolinethioamides as Recyclable Catalysts in the Enantioselective Solvent-Free Inter- and Intramolecular Aldol Reactions
  作者：Diana Almaşi、Diego A. Alonso、Carmen Nájera

  DOI：10.1002/adsc.200800430

  日期：2008.11.3

  and direct anti-aldol reaction of aliphatic ketones with aromatic aldehydes catalyzed by recyclable L-prolineamides and L-prolinethioamides 3 is studied. The L-prolinethioamide 3d (5 mol%), derived from L-Pro and (R)-1-aminoindane, is the most efficient catalyst for this process affording the anti-aldol adducts in high yields with excellent diastereo- and enantioselectivities (up to >98/2 dr, up to

  研究了可回收的L-脯氨酸酰胺和L-脯氨酸硫酰胺3催化的脂肪族酮与芳族醛的无溶剂不对称和直接的抗醛醇缩合反应。衍生自L-Pro和（R）-1-氨基茚满的L-脯氨酸硫代酰胺3d（5 mol％）是该方法最有效的催化剂，可提供高收率的抗醛醇加合物，并具有出色的非对映体和对映体选择性（up在0°C或室温下达到> 98/2 dr，最高可达98％ee）。脯氨酸硫酰胺3d是有效的有机催化剂，可用于首个不对称，无溶剂的分子内Hajos-Parrish-Eder-Sauer-Wiechert反应，其对映选择性（据报道高达88％ee）与有机溶剂中的对映选择性相当或更高。而且，有机催化剂3d可以通过简单的酸/碱萃取容易地回收和再利用。
• Water<i>versus</i>Solvent-Free Conditions for the Enantioselective Inter- and Intramolecular Aldol Reaction Employing L-Prolinamides and L-Prolinethioamides as Organocatalysts
  作者：Diana Almaşi、Diego A. Alonso、Andrea-Nekane Balaguer、Carmen Nájera

  DOI：10.1002/adsc.200800814

  日期：2009.5

  Abstractmagnified imageOrganocatalysts 1, derived from L‐proline and (1S,2R)‐cis‐1‐aminoindan‐2‐ol or (R)‐1‐aminoindane, are evaluated as promoters in the direct asymmetric aldol reaction between ketones and aromatic aldehydes in the presence of water and under solvent‐free reaction conditions. L‐Prolinethioamides 1c and 1d exhibited higher enantioselectivity than the corresponding prolinamides 1a and 1b in the model aldol reaction between cyclohexanone and 4‐nitrobenzaldehyde in the presence of 4‐nitrobenzoic acid as cocatalyst. In particular, L‐prolinethioamide 1d (5 mol%), derived from L‐proline and (R)‐1‐aminoindane, is shown as the most efficient organocatalyst studied promoting the direct aldol reaction of cycloalkyl, alkyl, and α‐functionalized ketones with aromatic aldehydes in the presence of water and under solvent‐free reaction conditions employing only 2 equivalents of nucleophile. Generally, anti‐aldol products are obtained in high yields and excellent diastereo‐ and enantioselectivities (up to >98/2 anti/syn, up to 98% ee). Solvent‐free conditions give slightly higher dr and ee than using water as solvent. In addition, organocatalyst 1d can be easily recovered by extractive work‐up and reused. Prolinethioamide 1d (5 mol%) in combination with 4‐NO2C6H4CO2H (5 mol%) is also a very effective organocatalytic system for the asymmetric solvent‐free intramolecular Hajos–Parrish–Eder–Sauer–Wiechert reaction with comparable or higher levels of enantioselectivity (up to 88% ee) to other reported catalysts in organic solvents.