(+/-)-threo-2-acetylamino-3-indol-3-yl-butyric acid | 33457-96-4

• 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: (+/-)-threo-2-acetylamino-3-indol-3-yl-butyric acid
• 英文别名: (+/-)-threo-2-Acetylamino-3-indol-3-yl-buttersaeure；(2S,3S)-2-acetamido-3-(1H-indol-3-yl)butanoic acid
• CAS: 33457-96-4；33458-53-6；34308-77-5；38871-55-5；38871-56-6
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: BJZSSQKRXOYXCT-SDBXPKJASA-N

物化性质

• 沸点：
  568.5±45.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-threo-2-acetylamino-3-indol-3-yl-butyric acid 以44%的产率得到(2S,3S)-β-methyltryptophan
  参考文献：
  名称：

  链黑素生物合成。4. 色氨酸代谢细节

  摘要：

  已经阐明了导致链黑素生物合成的色氨酸代谢的细节。这些包括鉴定 L-色氨酸作为天然前体，分离该途径中的早期中间体，以及使用 ^(15)N-^(13)C 异核自旋耦合来阐明导致 4 -苯基吡啶甲酸部分（CD环）。额外的喂养显然消除了导致喹啉环的所有已知途径的可能参与；提出了这部分（AB 环）起源的建议。

  DOI：

  10.1021/ja00525a040
• 作为产物：
  描述：

  ammonium (3-indolylethylidene)acetamidomalonate 以 吡啶 、 水 为溶剂， 反应 5.0h， 以30%的产率得到treo-2-acetamido-3-(3-indolyl)butyric acid
  参考文献：
  名称：

  链黑素生物合成。4. 色氨酸代谢细节

  摘要：

  已经阐明了导致链黑素生物合成的色氨酸代谢的细节。这些包括鉴定 L-色氨酸作为天然前体，分离该途径中的早期中间体，以及使用 ^(15)N-^(13)C 异核自旋耦合来阐明导致 4 -苯基吡啶甲酸部分（CD环）。额外的喂养显然消除了导致喹啉环的所有已知途径的可能参与；提出了这部分（AB 环）起源的建议。

  DOI：

  10.1021/ja00525a040

文献信息

• Streptonigrin biosynthesis. 4. Details of the tryptophan metabolism
  作者：Steven J. Gould、Chiu Chin Chang、Dennis S. Darling、John D. Roberts、Michael Squillacote

  DOI：10.1021/ja00525a040

  日期：1980.2

  the metabolism of tryptophan leading to the biosynthesis of streptonigrin have been elucidated. These include identification of L-tryptophan as the natural precursor, the isolation of an early intermediate in the pathway, and the use of ^(15)N-^(13)C heteronuclear spin couplings to eludicate the N-C bond cleavage leading to the 4-phenylpicolinic acid portion (C-D rings). Additional feedings have apparently

  已经阐明了导致链黑素生物合成的色氨酸代谢的细节。这些包括鉴定 L-色氨酸作为天然前体，分离该途径中的早期中间体，以及使用 ^(15)N-^(13)C 异核自旋耦合来阐明导致 4 -苯基吡啶甲酸部分（CD环）。额外的喂养显然消除了导致喹啉环的所有已知途径的可能参与；提出了这部分（AB 环）起源的建议。
• 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
• 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.