(2R,3R)-<1-(1(S)-phenylethyl)-2-methylpyrrolidin-3-yl>carboxylic acid methyl ester | 143878-88-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,3R)-<1-(1(S)-phenylethyl)-2-methylpyrrolidin-3-yl>carboxylic acid methyl ester
• 英文别名: Methyl (2R,3R)-2-methyl-1-[(1S)-1-phenylethyl]-3-pyrrolidinecarboxylate；methyl (2R,3R)-2-methyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxylate
• CAS: 143878-88-0
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: QVKPXSULPYUNBF-OUCADQQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl 2-acetylcyclopropanecarboxylate 在 镍 氢气 作用下， 以 甲苯 为溶剂， 生成 (2R,3R)-<1-(1(S)-phenylethyl)-2-methylpyrrolidin-3-yl>carboxylic acid methyl ester
  参考文献：
  名称：

  与手性可氢解胺的不对称合成。环状β-烯氨基酯还原为2,3-二取代吡咯烷的非对映选择性路线

  摘要：

  由手性α-甲基苄基胺制得的环状β-烯胺酯被非对映异构体过量地催化还原。

  DOI：

  10.1016/s0040-4039(00)74247-x

文献信息

• Design and Synthesis of 56 Shape‐Diverse 3D Fragments
  作者：Thomas D. Downes、S. Paul Jones、Hanna F. Klein、Mary C. Wheldon、Masakazu Atobe、Paul S. Bond、James D. Firth、Ngai S. Chan、Laura Waddelove、Roderick E. Hubbard、David C. Blakemore、Claudia De Fusco、Stephen D. Roughley、Lewis R. Vidler、Maria Ann Whatton、Alison J.‐A. Woolford、Gail L. Wrigley、Peter O'Brien

  DOI：10.1002/chem.202001123

  日期：2020.7.22

  generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under‐represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning

  基于片段的药物发现现已广泛应用于制药行业的先导化合物开发。然而，片段筛选集合通常主要由扁平的二维分子组成。在此，我们描述了设计和合成 56 个 3D 二取代吡咯烷和哌啶片段的工作流程，这些片段占据了片段空间中代表性不足的区域（如主惯性矩 (PMI) 分析所示）。该片段集合的一个关键且独特的基础设计特征是在合成和合成之前对片段形状和构象多样性进行评估（通过考虑比全局最小能量构象异构体的能量高出高达 1.5 kcal mol -1的构象）。也用于选择合成目标。3D 片段被设计为包含合适的合成手柄，以供将来的片段精加工使用。最后，通过将我们的 3D 片段与六个商业图书馆进行比较，很明显我们的馆藏具有较高的三维度和形状多样性。
• Enamino Ester Reduction: A Short Enantioselective Route to Pyrrolizidine and Indolizidine Alkaloids. Synthesis of (+)-Laburnine, (+)-Tashiromine, and (−)-Isoretronecanol
  作者：Olivier David、Jérôme Blot、Christian Bellec、Marie-Claude Fargeau-Bellassoued、Gjergj Haviari、Jean-Pierre Célérier、Gérard Lhommet、Jean-Claude Gramain、Daniel Gardette

  DOI：10.1021/jo982169p

  日期：1999.4.1

  over Pd/C gave rise to the higher diastereoselectivity and mainly afforded the unexpected anti addition product (e.d. 84%). The scope of these reductions has been extended to the synthesis of three pyrrolizidine or indolizidine alkaloids: (+)-tashiromine, (+)-laburnine, and (-)-isoretronecanol. Syntheses of these natural products, starting from chiral beta-enamino diesters, were achieved in a short and

  由于源自（S）-α-甲基苄胺的手性诱导，各种手性吡咯烷四取代的β-烯氨基酯以良好或中等的非对映选择性被催化或化学还原。使用环内双键化合物，使用PtO（2）作为加氢催化剂可获得最佳结果，并导致主要的合成加成产物（ed 90％）。在环外双键化合物的情况下，在Pd / C上进行氢化会产生更高的非对映选择性，并主要提供意想不到的抗加成产物（84％）。这些减少的范围已扩展到三种吡咯烷或生物碱的合成：（+）-tashiromine，（+）-laburnine和（-）-异戊烯醇。从手性β-烯胺二酯开始合成这些天然产物，
• Catalysis of 3-Pyrrolidinecarboxylic Acid and Related Pyrrolidine Derivatives in Enantioselective <i>anti</i>-Mannich-Type Reactions:  Importance of the 3-Acid Group on Pyrrolidine for Stereocontrol
  作者：Haile Zhang、Susumu Mitsumori、Naoto Utsumi、Masanori Imai、Noemi Garcia-Delgado、Maria Mifsud、Klaus Albertshofer、Paul Ha-Yeon Cheong、K. N. Houk、Fujie Tanaka、Carlos F. Barbas

  DOI：10.1021/ja074907+

  日期：2008.1.1

  The development of enantioselective anti-selective Mannich-type reactions of aldehydes and ketones with imines catalyzed by 3-pyrrolidinecarboxylic acid and related pyrrolidine derivatives is reported in detail. Both (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid and (R)-3-pyrrolidinecarboxylic acid efficiently catalyzed the reactions of aldehydes with alpha-imino esters under mild conditions and afforded anti-Mannich products with high diastereo- and enantioselectivities (anti/syn up to 99:1, up to >99% ee). For the reactions of ketones with a-imino esters, (R)-3-pyrrolidinecarboxylic acid was an efficient catalyst (anti/syn up to >99:1, up to 99% ee). Evaluation of a series of pyrrolidine-based catalysts indicated that the acid group at the beta-position of the pyrrolidine ring of the catalyst played an important role in forwarding the carbon-carbon bond formation and in directing anti-selectivity and enantioselectivity.