(S)-(S)-5-amino-2-((tert-butoxycarbonyl)amino)-5-oxopentanoic (isobutyl carbonic) anhydride | 105888-44-6

• 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)-(S)-5-amino-2-((tert-butoxycarbonyl)amino)-5-oxopentanoic (isobutyl carbonic) anhydride
• CAS: 105888-44-6
• 化学式: C₁₅H₂₆N₂O₇
• 分子量: 346.381
• InChiKey: SCTWVYDEQRYRAA-JTQLQIEISA-N

物化性质

• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.48
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  134.02
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-(S)-5-amino-2-((tert-butoxycarbonyl)amino)-5-oxopentanoic (isobutyl carbonic) anhydride 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -10.0~40.0 ℃ 、392.24 kPa 条件下， 反应 129.0h， 生成 Boc-Gln-R-EtA-Hyp-MeA-Phol
  参考文献：
  名称：

  Emerimicins III 和 IV 及其乙基丙氨酸 12 差向异构体。促进化学酶合成及其溶液结构的定性评价

  摘要：

  peptaibol 抗生素，emerimicin III 和 IV（Ac-Phe 1 -MeA 2 -MeA 3 -MeA 4 -Val 5 -Gly 6 -Leu 7 -MeA 8 -MeA 9 - Hyp 10 -Gln 11 -R-EtA 12 -Hyp 13 -Xxx 14 -Phol 15 ，其中 Xxx=Ala for emerimicin III 和 Xxx=MeA for emerimicin IV) 和它们的 EtA 12 差向异构体已经使用包括溶液相片段缩合和最终木瓜蛋白酶介导的偶联的组合方法合成1-6 和 7-15 片段

  DOI：

  10.1021/ja00037a010
• 作为产物：
  描述：

  Boc-L-谷氨酰胺 、 氯甲酸异丁酯 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.02h， 生成 (S)-(S)-5-amino-2-((tert-butoxycarbonyl)amino)-5-oxopentanoic (isobutyl carbonic) anhydride
  参考文献：
  名称：

  简便的手性N保护的β-氨基醇的合成。

  摘要：

  通过在有机/水介质中通过NaBH 4还原N-保护的α-氨基酸的混合酸酐可以容易地获得手性的N-保护的β-氨基醇。由N-保护的天冬氨酸的侧链或主链还原得到的醇以良好的产率转化为内酯。

  DOI：

  10.1016/s0040-4039(00)92121-x

文献信息

• Short analogs and mimetics of human urocortin 3 display antidepressant effects in vivo
  作者：Kinga Rákosi、Tanaka Masaru、Márta Zarándi、Gyula Telegdy、Gábor K. Tóth

  DOI：10.1016/j.peptides.2014.09.023

  日期：2014.12

  Peptide analogs of urocortin 3[36-38] (Ucn 3[36-38]), obtained with deletion or replacement of amino acids of the original human urocortin 3 sequence, were designed, synthesized, and tested in vivo for treatment of depression. Based on the results of the biological tests of the peptide analogs, several new peptidomimetics of the above short analogs of urocortin 3, including urea- and azapeptides, were also designed and synthesized and found to preserve the antidepressant-like effect of the 38 amino acid long original neuropeptide. The molecular modifications of urocortin 3[36-38] led to an improved understanding of the relationship between molecular structure and biological activity of this peptide, and the novel peptidomimetics could be further tested for possible clinical treatment of depression. (C) 2014 Elsevier Inc. All rights reserved.
• Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity
  作者：Joseph P. Sanchez、John M. Domagala、Carl L. Heifetz、Stephen R. Priebe、Josephine A. Sesnie、Ashok K. Trehan

  DOI：10.1021/jm00088a011

  日期：1992.5

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).
• Khalikov, Sh. Kh.; Alieva, S. V.; Ashurov, S. G., Russian Journal of Bioorganic Chemistry, 1994, vol. 20, # 4, p. 202 - 212
  作者：Khalikov, Sh. Kh.、Alieva, S. V.、Ashurov, S. G.

  DOI：——

  日期：——
• Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
  作者：Hubert Josien、Solange Lavielle、Alie Brunissen、Monique Saffroy、Yvette Torrens、Jean-Claude Beaujouan、Jacques Glowinski、Gerard Chassaing

  DOI：10.1021/jm00037a009

  日期：1994.5

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.
• Structure activity studies on the C-terminal hexapeptide of substance P with modifications at the glutaminyl and methioninyl residues
  作者：Constantine Poulos、George Stavropoulos、John R. Brown、Christopher C. Jordan

  DOI：10.1021/jm00391a041

  日期：1987.8

  Analogues of [Orn6]-SP6-11 have been synthesized in which the SCH3 group of the Met11 side chain is replaced by other functional groups, such as (CH2)2NH2, COOH, CONH2, and COOR, which have basic, acid, or neutral character and which may act as either H-bonding donors or H-bonding acceptors. These analogues were tested in guinea pig ileum and rat colon muscularis mucosae, in vitro. Substitution of Lys, Gln, or Glu at position 11 caused a marked reduction in biological activity in both tissues. In contrast, the glutamate benzyl ester analogue had only slightly reduced activity in the guinea pig ileum and an increased (4.7 times) activity in the rat colon. It is concluded that charged groups in the side chain at position 11 of SP6-11 reduce the biological activity of SP hexapeptide.