(S)-2-(3-methyl-1-morpholino-1-oxobutan-2-yl)isoindoline-1,3-dione | 154462-94-9

• 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)-2-(3-methyl-1-morpholino-1-oxobutan-2-yl)isoindoline-1,3-dione
• 英文别名: (S)-N-phtaloylvalylmorpholine；2-[(1S)-2-methyl-1-(morpholine-4-carbonyl)propyl]isoindoline-1,3-dione；2-[(2S)-3-methyl-1-morpholin-4-yl-1-oxobutan-2-yl]isoindole-1,3-dione
• CAS: 154462-94-9
• 化学式: C₁₇H₂₀N₂O₄
• 分子量: 316.357
• InChiKey: ZEASYPCDBWFIAM-AWEZNQCLSA-N

物化性质

• 沸点：
  497.6±40.0 °C(predicted)
• 密度：
  1.284±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(3-methyl-1-morpholino-1-oxobutan-2-yl)isoindoline-1,3-dione 在 lithium aluminium tetrahydride 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 95.0h， 生成 (S)-1-isopropyl-N-methyl-2-morpholinoethylamine
  参考文献：
  名称：

  Enantioselective Aldol and Michael Additions of Achiral Enolates in the Presence of Chiral Lithium Amides and Amines

  摘要：

  目前已经充分确定，锂烯醇盐及其类似衍生物通常以非共价键结合而成的复杂结构（“超分子”）存在。特别是，锂烯醇盐聚集形成二聚体、四聚体和高阶寡聚体，其金属中心可能被溶剂分子或螯合配体络合。此外，烯醇盐的阴离子部分可能与二级胺等弱酸形成氢键。而且，这些超分子在锂烯醇盐的合成反应中可能是产物形成物种。本文描述了我们观察到的将手性胺或手性锂酰胺暂时掺入非手性锂烯醇盐聚集体（在水中处理时这种相互作用被简单破坏！）从而产生手性富集产物的现象。特别是，在几种由(S)-缬氨酸或(R,R)-酒石酸衍生的手性胺（或它们的锂酰胺）存在下，实现了非手性烯醇盐与非手性的醛或非手性硝基烯烃的立体选择性羟醛缩合反应和迈克尔加成反应。最后，本报告展示了手性α-氨基烷氧基导向的邻位锂化在对映选择性合成中的潜在应用价值。

  DOI：

  10.1055/s-1993-26041
• 作为产物：
  描述：

  2-酞酰亚胺基-3-甲基丁酸 在 氯化亚砜 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 28.0h， 生成 (S)-2-(3-methyl-1-morpholino-1-oxobutan-2-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Enantioselective Aldol and Michael Additions of Achiral Enolates in the Presence of Chiral Lithium Amides and Amines

  摘要：

  目前已经充分确定，锂烯醇盐及其类似衍生物通常以非共价键结合而成的复杂结构（“超分子”）存在。特别是，锂烯醇盐聚集形成二聚体、四聚体和高阶寡聚体，其金属中心可能被溶剂分子或螯合配体络合。此外，烯醇盐的阴离子部分可能与二级胺等弱酸形成氢键。而且，这些超分子在锂烯醇盐的合成反应中可能是产物形成物种。本文描述了我们观察到的将手性胺或手性锂酰胺暂时掺入非手性锂烯醇盐聚集体（在水中处理时这种相互作用被简单破坏！）从而产生手性富集产物的现象。特别是，在几种由(S)-缬氨酸或(R,R)-酒石酸衍生的手性胺（或它们的锂酰胺）存在下，实现了非手性烯醇盐与非手性的醛或非手性硝基烯烃的立体选择性羟醛缩合反应和迈克尔加成反应。最后，本报告展示了手性α-氨基烷氧基导向的邻位锂化在对映选择性合成中的潜在应用价值。

  DOI：

  10.1055/s-1993-26041

文献信息

• Synthesis, structural aspects and nonlinear optical properties of novel phthalimide derivatives: theoretical and experimental approach
  作者：Anil K. Singh、Ram Kishan、Vijay Bahadur、Narayanasamy Vijayan、Vadivelu Balachandran、Hemandra K. Tiwari、Brajendra K. Singh、Brijesh Rathi

  DOI：10.1002/poc.3287

  日期：2014.6

  Novel phthalimides (1, 2, 3) possessing variability of cyclic amines have been synthesized and characterized by analytical and spectroscopic techniques. Phthalimide 1 and 2 crystallized in a triclinic system with space group Pī; however, an orthorhombic system with a chiral space group of P212121 was observed for 3 possessing piperidine cyclic amine. The hydrogen atoms attached to the central chiral

  新颖邻苯二甲酰亚胺（1，2，3）环胺的具有可变性，已经合成和表征通过分析和光谱技术。邻苯二甲酰亚胺1和2与空间群的三斜晶系结晶P I; 然而，对于具有哌啶环胺的3，观察到具有P2 1 2 1 2 1手性空间基团的正交晶系。附着在中央手性碳原子上的氢原子彼此反向取向，从而使空间排斥力最小。1中存在CHH··O氢键，2，3启用几个超分子结构的建筑。超极化197.6096德拜埃2计算出的1被发现是比超极化高，138.0836和165.2521德拜埃2为测量2和3分别。随后，邻苯二甲酰亚胺（1，2，3）被评定为二次谐波生成（SHG）响应，并且可忽略的响应记录1和2 ; 但是3显示出14.2 mV的显着响应。除无心结构外，在3中确定的螺旋结构基序可能是其增强的SHG反应的原因。版权所有©2014 John Wiley＆Sons，Ltd.
• Design, synthesis and biological evaluation of functionalized phthalimides: A new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite
  作者：Anil K. Singh、Vinoth Rajendran、Akansha Pant、Prahlad C. Ghosh、Neelu Singh、N. Latha、Sandeep Garg、Kailash C. Pandey、Brajendra K. Singh、Brijesh Rathi

  DOI：10.1016/j.bmc.2015.02.029

  日期：2015.4

  Phthalimides functionalized with cyclic amines were synthesized, characterized and screened for their in vitro antimalarial efficacy against Plasmodium falciparum (Pf3D7). Of all the listed phthalimides evaluated, 14 and 24 were identified as potent antimalarial agents as advocated by assessment of their ability to inhibit [H-3] hypoxanthine incorporation in the nucleic acid of parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90 h and an enhanced antimalarial effect was noticed with increase in time to great extent. A reduction in IC50 values was observed with increase in exposure time of the parasite to the compounds. A symmetric phthalimide, 24 possessing piperazine as linker unit was identified as the most potent antimalarial agent with IC50 values of 5.97 +/- 0.78, 2.0 +/- 1.09 and 1.1 +/- 0.75 mu M on incubation period of 42, 60 and 90 h, respectively. The abnormal morphologies such as delay in developmental stages, growth arrest and condensed nuclei of parasite were observed with the aid of microscopic studies upon exposure with 14 and 24. The evaluation of 14 and 24 against chloroquine resistant strain, (Pf7GB) of P. falciparum afforded IC50 values, 13.29 +/- 1.20 and 7.21 +/- 0.98 mu M, respectively. The combination of 24 with artemisinin (ART) showed enhanced killing of parasite against Pf3D7. Further, all phthalimides were evaluated for their activity against falcipain-2 (FP2), a major hemoglobinase of malarial parasite. The enzymatic assay afforded 6 as most active member against FP2. To the best of our knowledge this is the initial study represents phthalimide protected amino acids functionalized with cyclic amines as potent antimalarial agents. (C) 2015 Elsevier Ltd. All rights reserved.
• Enantioselective Aldol and Michael Additions of Achiral Enolates in the Presence of Chiral Lithium Amides and Amines
  作者：Eusebio Juaristi、Albert K. Beck、Jesper Hansen、Thomas Matt、Triptikumar Mukhopadhyay、Malgorzata Simson、Dieter Seebach

  DOI：10.1055/s-1993-26041

  日期：——

  It is now well established that lithium enolates and analogous derivatives generally exist as complex structures held together by noncovalent bonds ("supramolecules"). In particular, Li enolates aggregate to give dimers, tetramers, and higher oligomers, whose metal centers may be complexed by solvent molecules or chelating ligands. In addition, the anionoid part of the enolates may hydrogen-bond to weak acids such as secondary amines. Furthermore, such supramolecules can be product-forming species in synthetic reactions of Li enolates. This paper describes our observations of the temporary incorporation of chiral amines or chiral lithium amides into achiral lithium enolate aggregates (an interaction which is simply broken during aqueous workup!) to give enantiomerically enriched products. In particular, enantioselective aldol and Michael additions between achiral enolates and achiral aldehydes or achiral nitroolefins have been achieved in the presence of several chiral amines (or their lithium amides) derived from (S)-valine or (R,R)-tartaric acid. Finally, this report demonstrates the potential usefulness in asymmetric synthesis of ortho lithiation directed by chiral α-aminoalkoxides.

  目前已经充分确定，锂烯醇盐及其类似衍生物通常以非共价键结合而成的复杂结构（“超分子”）存在。特别是，锂烯醇盐聚集形成二聚体、四聚体和高阶寡聚体，其金属中心可能被溶剂分子或螯合配体络合。此外，烯醇盐的阴离子部分可能与二级胺等弱酸形成氢键。而且，这些超分子在锂烯醇盐的合成反应中可能是产物形成物种。本文描述了我们观察到的将手性胺或手性锂酰胺暂时掺入非手性锂烯醇盐聚集体（在水中处理时这种相互作用被简单破坏！）从而产生手性富集产物的现象。特别是，在几种由(S)-缬氨酸或(R,R)-酒石酸衍生的手性胺（或它们的锂酰胺）存在下，实现了非手性烯醇盐与非手性的醛或非手性硝基烯烃的立体选择性羟醛缩合反应和迈克尔加成反应。最后，本报告展示了手性α-氨基烷氧基导向的邻位锂化在对映选择性合成中的潜在应用价值。