乙酰氨基丙二酸二苄酯 | 51887-51-5

• 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
• 中文名称: 乙酰氨基丙二酸二苄酯
• 英文名称: dibenzyl acetamidomalonate
• 英文别名: Dibenzyl acetamidopropanedioate；dibenzyl 2-acetamidopropanedioate
• CAS: 51887-51-5
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.364
• InChiKey: NPGCZPNVOKJINN-UHFFFAOYSA-N

物化性质

• 沸点：
  500.2±40.0 °C(Predicted)
• 密度：
  1.224

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  乙酰氨基丙二酸二苄酯 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 0.92h， 生成 乙酰氨基丙二酸二甲酯
  参考文献：
  名称：

  Synthesis and decarboxylation of Δ²-cephem-4,4-dicarboxylic acids

  摘要：

  青霉素V经过14个步骤转化为具有C-3处氢、C-2处氢或乙基，以及C-4处两个甲氧羰基、两个苄氧羰基或一个甲氧羰基和一个苄氧羰基取代基的Δ2-头孢菌素。通过碱性水解（对甲酯类）或氢解（对苄酯类）去保护这些Δ2-头孢菌素-4,4-二羧酸酯，在所有情况下都导致Δ2-头孢菌素-4,4-二羧酸或Δ2-头孢菌素-4,4-二羧酸单酯的快速脱羧。C-2处为氢时，用1当量碱水解二甲酯酯类产生Δ2-头孢菌素。用2当量碱，并且所有化合物C-2处为甲基时，水解或氢解得到4α-取代的Δ2-头孢菌素。 相比之下，更简单的苄或甲基乙酰胺丙二酸酯可以轻松去保护以得到稳定的丙二酸。使用半经验（AM1）和从头算（3-21G）分子轨道计算研究了脱羧难易度差异的原因。发现未离子化的头孢菌素或乙酰胺丙二酸的脱羧能垒较高（35-40 kcal mol-1）。尽管乙酰胺丙二酸的单负离子保留了较高的能垒，但Δ2-头孢菌素丙二酸的异构单负离子脱羧能垒仅为2 kcal mol-1。关键词：巯基氮杂环丙酮酮，溴丙二酸酯，分子轨道计算，亚氧化物，氢解。

  DOI：

  10.1139/v01-100
• 作为产物：
  描述：

  二苄基马来酸酯 在 盐酸 、 溶剂黄146 、 锌 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 1.33h， 生成 乙酰氨基丙二酸二苄酯
  参考文献：
  名称：

  Synthesis and decarboxylation of Δ²-cephem-4,4-dicarboxylic acids

  摘要：

  青霉素V经过14个步骤转化为具有C-3处氢、C-2处氢或乙基，以及C-4处两个甲氧羰基、两个苄氧羰基或一个甲氧羰基和一个苄氧羰基取代基的Δ2-头孢菌素。通过碱性水解（对甲酯类）或氢解（对苄酯类）去保护这些Δ2-头孢菌素-4,4-二羧酸酯，在所有情况下都导致Δ2-头孢菌素-4,4-二羧酸或Δ2-头孢菌素-4,4-二羧酸单酯的快速脱羧。C-2处为氢时，用1当量碱水解二甲酯酯类产生Δ2-头孢菌素。用2当量碱，并且所有化合物C-2处为甲基时，水解或氢解得到4α-取代的Δ2-头孢菌素。 相比之下，更简单的苄或甲基乙酰胺丙二酸酯可以轻松去保护以得到稳定的丙二酸。使用半经验（AM1）和从头算（3-21G）分子轨道计算研究了脱羧难易度差异的原因。发现未离子化的头孢菌素或乙酰胺丙二酸的脱羧能垒较高（35-40 kcal mol-1）。尽管乙酰胺丙二酸的单负离子保留了较高的能垒，但Δ2-头孢菌素丙二酸的异构单负离子脱羧能垒仅为2 kcal mol-1。关键词：巯基氮杂环丙酮酮，溴丙二酸酯，分子轨道计算，亚氧化物，氢解。

  DOI：

  10.1139/v01-100

文献信息

• Maier, Ludwig, Phosphorus and Sulfur and the Related Elements, 1983, vol. 14, p. 295 - 322
  作者：Maier, Ludwig

  DOI：——

  日期：——
• Spoendlin, Christoph; Tamm, Christoph, Heterocycles, 1989, vol. 28, # 1, p. 453 - 465
  作者：Spoendlin, Christoph、Tamm, Christoph

  DOI：——

  日期：——
• Novel sst₄-Selective Somatostatin (SRIF) Agonists. 3. Analogues Amenable to Radiolabeling
  作者：Judit Erchegyi、Beatrice Waser、Jean-Claude Schaer、Renzo Cescato、Jean François Brazeau、Jean Rivier、Jean Claude Reubi

  DOI：10.1021/jm030245x

  日期：2003.12.1

  After our discovery that H-c [Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8) had high affinity and marginal selectivity for human sst(3) (part 2 of this series: Erchegyi et al. J. Med. Chem., preceding paper in this issue)(11) and that H-c[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (ODT-8, 3) had high affinity and marginal selectivity for human sst(4), that H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH had high affinity for all sst's except for sst(1), and that H-c[Cys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH had high affinity for sst(4) (IC50 = 2.1 nM), with more than 50-fold selectivity toward the other receptors (parts 1 and 2 of this series: Rivier et al. and Erchegyi et al. J Med. Chem., preceding papers in this issue), we found H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH (OLT-8,2), H-c[Cys-Phe-Phe-L-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (4) and H-c[Cys-Phe-Phe-D-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (5) to have very high affinity for sst(4) (IC50 = 0.7, 1.8, and 4.0 nM, respectively) and 5- to 10-fold selectivity versus the other sst's. From earlier work, we concluded that an L-amino acid at position 8 and a tyrosine or 4-aminophenylalanine substitution at position 7 may lead to high sst(4) selectivity. In fact, [Tyr(7)]-2 (6) and [Tyr(7)]-3 (7) show ca. 5-fold selectivity for sst(4), and [Aph(7)]-2 (8) and [Aph(7)]-3 (9) have high sst(4) affinity (IC50 = 1.2 and 0.88 nM, respectively) and selectivity, suggesting that indeed an L-residue at position 8 will direct selectivity toward sst(4) Unexpectedly, [Ala(7)]-2 (10) and [Ala(7)]-3 (11) have very high sst(4) affinity (IC50 = 0.84 and 0.98 nM, respectively) and selectivity (>600- and 200-fold, respectively). The combination of Tyr(2) and DTrp(8) in analogues 14 and 22 did not affect the affinity of the analogues for sst(4) (IC50 = 1.2 and 1.1 nM, respectively) but resulted in loss of selectivity, whereas the combination of Tyr(2) and LTrp(8) in H-Tyr-c[Cys-Phe-Aph-Trp-Lys-Thr-Phe-Cys]-OH (13) and H-Tyr-c[Cys-Phe-Ala-Trp-Lys-Thr-Phe-Cys]-OH-(19) retained high affinity (IC50 = 1.9 and 1.98 nM, respectively) and sst(4) selectivity (>50 and >250, respectively). Interestingly, the same substitutions at positions 2 and 7, with L-threo-beta-MeTrp at position 8, yielded a much less selective analogue (20). Carbamoylation of the N-terminus of most of these analogues resulted in slightly improved affinity, selectivity, or both. Other amino acid substitutions in this series, such as those with Amp (25, 26), Orn (27), or LAmp (29) at position 7, were also tolerated but with a 2- to Mold loss of affinity and concomitant loss of selectivity. Analogous peptides with a tyrosine at position 11 (31-36) were less selective than the corresponding peptides with a tyrosine at position 2. Several analogues in this series compared favorably with the non-peptide L-803,087 (37) in terms of affinity and selectivity. Analogues 8, 10, and 21 potently inhibited the forskolin-stimulated cAMP production in sst(4)-transfected cells, therefore acting as full agonists. Cold monoiodination of 19 yielded 21, with retention of high sst(4) selectivity and affinity (IC50 = 3.5 nM). (125)Iodinated 19 selectively binds to sst(4)-transfected cells but not to sst(1-3)- or sst(5)-transfected cells.Binding in sst(4)-transfected cells was completely displaced by SRIF-28 or the sst(4)-selective L-803,087.
• The Synthesis of the 2-Amino-3-(3-indolyl)-butyric Acids (β-Methyltryptophans)
  作者：H. R. Snyder、Donald S. Matteson

  DOI：10.1021/ja01566a050

  日期：1957.5
• Aminoketones. I. The Preparation of α-Aminoketones from Di-t-butyl Acetamidomalonate²
  作者：Anthony W. Schrecker、Mary M. Trail

  DOI：10.1021/ja01555a045

  日期：1958.11