dimethyl L-2-(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)pentanedioate | 35457-98-8

• 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: dimethyl L-2-(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)pentanedioate
• 英文别名: dimethyl 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)pentanedioate；Dimethyl ester of N-phthalyl-L-glutamic acid；N-Phthaloylglutaminsaeuredimethylester；(S)-2-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)pentanedioic acid dimethyl ester；dimethyl (2S)-2-(1,3-dioxoisoindol-2-yl)pentanedioate
• CAS: 35457-98-8
• 化学式: C₁₅H₁₅NO₆
• 分子量: 305.287
• InChiKey: AGWBTFOIAUGNNH-NSHDSACASA-N

物化性质

• 沸点：
  436.8±35.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2925190090

反应信息

• 作为反应物：
  描述：

  dimethyl L-2-(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)pentanedioate 在 sodium amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以45%的产率得到反应停
  参考文献：
  名称：

  A Practical and Efficient Synthesis of Thalidomide via Na/Liquid NH₃ Methodology¹

  摘要：

  A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected L-glutamic acid diester via Na/ liquid (liq.) NH3 (-33 degrees C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.

  DOI：

  10.1021/op050129z
• 作为产物：
  描述：

  苯酐 在 氯化亚砜 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 24.0h， 生成 dimethyl L-2-(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)pentanedioate
  参考文献：
  名称：

  基因编码的赖氨酸，用于合成具有特定位点的赖氨酸二甲基化的蛋白质

  摘要：

  使用琥珀色抑制方法，N genetic-（4-叠氮基苯并氧羰基）-δ，ϵ-脱氢赖氨酸，一种赖氨酸前体在大肠杆菌中遗传编码。通过遗传整合，随后进行了两个连续的生物相容性反应，可以方便地合成具有位点特异性赖氨酸二甲基化的蛋白质。使用这种方法，已经合成了二甲基组蛋白H3和p53蛋白，并用于探测表观遗传酶的功能，包括组蛋白脱甲基酶LSD1和组蛋白乙酰转移酶Tip60。我们证实，LSD1对H3K4me2和H3K9me2具有催化活性，但对H3K36me2具有惰性，p53 K372处的甲基化直接激活Tip60在p53 K120处的催化乙酰化作用。

  DOI：

  10.1002/anie.201609452

文献信息

• Diastereoselective palladium-catalyzed C(sp³)–H cyanomethylation of amino acid and carboxylic acid derivatives
  作者：Sumit Garai、Krishna Gopal Ghosh、Ashik Biswas、Sushobhan Chowdhury、Devarajulu Sureshkumar

  DOI：10.1039/d2cc03106j

  日期：——

  8-aminoquinoline-directed α-amino acids using inexpensive chloroacetonitrile. Iodoacetonitrile generated in situ from chloroacetonitrile reacts with methylene C(sp3)–H bonds of α-amino acids with excellent diastereoselectivity, enabling access to a wide range of important γ-cyano-α-amino acids. Our protocol works well with different amino acid and carboxylic acid derivatives with good chemical yields

  在本研究中，我们报告了一种使用廉价氯乙腈对 8-氨基喹啉导向的 α-氨基酸进行 Pd 催化的亚甲基 β-C(sp 3 )-H 氰甲基化的有效方案。由氯乙腈原位生成的碘乙腈与 α-氨基酸的亚甲基 C(sp 3 )-H 键反应，具有优异的非对映选择性，能够获得各种重要的 γ-氰基-α-氨基酸。我们的协议适用于不同的氨基酸和羧酸衍生物，具有良好的化学产率和高官能团耐受性。
• Thiothalidomides:  Novel Isosteric Analogues of Thalidomide with Enhanced TNF-α Inhibitory Activity
  作者：Xiaoxiang Zhu、Tony Giordano、Qian-sheng Yu、Harold W. Holloway、Tracy Ann Perry、Debomoy K. Lahiri、Arnold Brossi、Nigel H. Greig

  DOI：10.1021/jm030152f

  日期：2003.11.1

  Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-a secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity.
• Search for radioprotectors in the series of glutamic acid derivatives
  作者：G. G. Vatulina、T. N. Tuzhilkova、T. V. Matveeva、V. P. Krasnov、N. L. Burde、L. V. Alekseeva

  DOI：10.1007/bf01148642

  日期：1986.9
• A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation
  作者：Zhipeng A. Wang、Yu Zeng、Yadagiri Kurra、Xin Wang、Jeffery M. Tharp、Erol C. Vatansever、Willie W. Hsu、Susie Dai、Xinqiang Fang、Wenshe R. Liu

  DOI：10.1002/anie.201609452

  日期：2017.1.2

  Using the amber suppression approach, Nϵ‐(4‐azidobenzoxycarbonyl)‐δ,ϵ‐dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site‐specific lysine dimethylation. Using this approach, dimethyl‐histone H3 and p53 proteins have been synthesized and used to probe functions

  使用琥珀色抑制方法，N genetic-（4-叠氮基苯并氧羰基）-δ，ϵ-脱氢赖氨酸，一种赖氨酸前体在大肠杆菌中遗传编码。通过遗传整合，随后进行了两个连续的生物相容性反应，可以方便地合成具有位点特异性赖氨酸二甲基化的蛋白质。使用这种方法，已经合成了二甲基组蛋白H3和p53蛋白，并用于探测表观遗传酶的功能，包括组蛋白脱甲基酶LSD1和组蛋白乙酰转移酶Tip60。我们证实，LSD1对H3K4me2和H3K9me2具有催化活性，但对H3K36me2具有惰性，p53 K372处的甲基化直接激活Tip60在p53 K120处的催化乙酰化作用。
• A Practical and Efficient Synthesis of Thalidomide via Na/Liquid NH₃ Methodology¹
  作者：Ravi Varala、Srinivas R. Adapa

  DOI：10.1021/op050129z

  日期：2005.11.1

  A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected L-glutamic acid diester via Na/ liquid (liq.) NH3 (-33 degrees C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.