Boc-Gaba-OSu | 69038-04-6

• 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: Boc-Gaba-OSu
• 英文别名: 2,5-Dioxopyrrolidin-1-yl 4-(tert-butoxycarbonylamino)butanoate；(2,5-dioxopyrrolidin-1-yl) 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 69038-04-6
• 化学式: C₁₃H₂₀N₂O₆
• mdl: MFCD00624376
• 分子量: 300.312
• InChiKey: FZHPNVGBJRBWRE-UHFFFAOYSA-N

物化性质

• 熔点：
  110 °C
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.692
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-Gaba-OSu 在 三(三甲代甲硅烷基)亚磷酸盐 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以61%的产率得到阿仑膦酸
  参考文献：
  名称：

  阿仑膦酸盐、帕米膦酸盐和奈立膦酸盐的膦酸酯的合成

  摘要：

  研究了获得氨基双膦酸 (NBPs) pamidronate、alendronate 和 neridronate 膦酸酯的几种合成途径。一般指导原则是将 N 保护的氨基酸作为邻苯二甲酰亚胺酯或酰氯活化。发现琥珀酰亚胺酯的反应性较低并很快被废弃。当从 Boc 或 Cbz 保护的氨基酸开始时，会形成 γ-内酰胺。邻苯二甲酰亚胺 N-保护基团允许以高产率获得这三种 NBP 的烷基或芳基单酯、二酯（对称或非对称）和三酯。((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)。

  DOI：

  10.1002/ejoc.200601067
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 49.0h， 生成 Boc-Gaba-OSu
  参考文献：
  名称：

  分子伞调节多烯大环内酯类抗真菌药的选择性毒性。

  摘要：

  抗真菌多烯大环内酯类抗生素两性霉素B（AmB）和制霉菌素（NYS）通过ω-氨基酸接头与由亚精胺连接的脱氧胆酸或胆酸组成的双壁“分子伞”结合。“伞状”取代基的存在调节了抗生素的生物学特性，尤其是其选择性毒性。一些AmB伞结合物显示出与母体抗生素相当的体外抗真菌活性，但降低了哺乳动物的毒性，尤其是溶血活性。相反，NYS-伞状结合物的体外抗真菌活性大大降低，并且所有这些结合物均表现出比NYS选择性毒性差的作用。没有发现新型结合物的聚集状态和溶血活性之间的相关性。

  DOI：

  10.1021/acs.bioconjchem.8b00136

文献信息

• Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
  作者：Julia A. Pavlova、Zimfira Z. Khairullina、Andrey G. Tereshchenkov、Pavel A. Nazarov、Dmitrii A. Lukianov、Inna A. Volynkina、Dmitry A. Skvortsov、Gennady I. Makarov、Etna Abad、Somay Y. Murayama、Susumu Kajiwara、Alena Paleskava、Andrey L. Konevega、Yuri N. Antonenko、Alex Lyakhovich、Ilya A. Osterman、Alexey A. Bogdanov、Natalia V. Sumbatyan

  DOI：10.3390/antibiotics10050489

  日期：——

  bacterial ribosomes differs from that of CHL. By simulating the dynamics of CAM-Cn-TPP complexes with bacterial ribosomes, we proposed a possible explanation for the specificity of the action of these analogs in the translation process. CAM-C10-TPP and CAM-C14-TPP more strongly inhibit the growth of the Gram-positive bacteria, as compared to CHL, and suppress some CHL-resistant bacterial strains. Thus,

  在当前的工作中，我们在继续我们的最新研究的基础上，合成并研究了新的嵌合化合物，包括靶向核糖体的抗生素氯霉素（CHL）和膜穿透性阳离子三苯基phosph（TPP），它们通过不同长度的烷基连接。使用各种生化分析，我们表明这些CAM-Cn-TPP化合物与细菌核糖体结合，以与母体CHL类似的方式在体内和体外抑制蛋白质合成，并显着降低膜电位。与CAM-C4-TPP相似，细菌核糖体中CAM-C10-TPP和CAM-C14-TPP的作用方式与CHL不同。通过模拟细菌核糖体的CAM-Cn-TPP复合物的动力学，我们提出了这些类似物在翻译过程中作用的特异性的可能解释。与CHL相比，CAM-C10-TPP和CAM-C14-TPP更强烈地抑制革兰氏阳性细菌的生长，并抑制一些对CHL耐药的菌株。因此，我们已经表明CHL的TPP衍生物是针对细菌的核糖体和细胞膜的双重作用化合物。CAM-Cn-TPP化合物的TPP片段
• Decomposition of 1-(ω-aminoalkanoyl)guanidines under alkaline conditions
  作者：Albert Brennauer、Max Keller、Matthias Freund、Günther Bernhardt、Armin Buschauer

  DOI：10.1016/j.tetlet.2007.07.147

  日期：2007.9

  The decomposition of some NG-(ω-aminoalkanoyl)argininamides, which are key intermediates for the preparation of radiolabeled and fluorescent neuropeptide Y receptor ligands, prompted us to synthesize a small series of simple 1-(ω-aminoalkanoyl)guanidines, and to investigate these model compounds for stability in alkaline buffers. The degradation of acylguanidines was monitored by time resolved UV spectroscopy

  一些N G-（ω-氨基链烷酰基）精氨酰胺的分解，这是制备放射性标记和荧光神经肽Y受体配体的关键中间体，促使我们合成了一小批简单的1-（ω-氨基链烷酰基）胍，并且研究这些模型化合物在碱性缓冲液中的稳定性。通过时间分辨紫外光谱法监测酰基胍的降解。最不稳定的化合物1-（5-氨基戊酰基）胍以19 s的半衰期分解，生成哌啶-2-酮（25°C，pH 10.4）。相反，1-（6-氨基己基）胍的半衰期为7.7 h，与 碱性溶液中乙酰胍的水解（t 1/2 = 9.6 h）相当。
• NOVEL SEMI-SYNTHETIC GLYCOPEPTIDES AS ANTIBACTERIAL AGENTS
  申请人：Chu Daniel

  公开号：US20100105607A1

  公开（公告）日：2010-04-29

  Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of the a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; conversion of the amide group in amino acid-3 on these scaffolds to various acylamide, acylsulfonamide, acylsulfonylurea derivatives; aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.

  所描述的具有抗菌活性的半合成糖肽，特别是这里描述的半合成糖肽是通过对一种糖肽（化合物A、化合物B、化合物H或化合物C）进行化学修饰制备的，或者通过在酸性介质中水解氨基酸-4的二糖基团以得到氨基酸-4单糖基团；将单糖转化为氨基糖衍生物；用特定酰基对这些支架上氨基酸-4氨基取代糖基团上的氨基取代基进行酰化；将这些支架上氨基酸-3中的酰胺基团转化为各种酰胺、酰磺酰胺、酰磺酰脲衍生物；通过曼尼希反应在氨基酸-7上含有磺胺基或酰磺酰胺基团的取代基上进行氨甲基化；以及将这些支架上大环环上的酸基团转化为特定取代酰胺。还提供了合成这些化合物的方法，含有这些化合物的药物组合物，以及这些化合物用于治疗和/或预防疾病，特别是细菌感染的方法。
• Artificial ribonucleases 6. Ribonuclease activity of tetrapeptides based on amino acids involved in the catalytic site of RNase T1
  作者：L. S. Koroleva、A. A. Donina、N. V. Tamkovich、N. A. Kovalev、M. A. Zenkova、V. N. Sil’nikov

  DOI：10.1007/s11172-006-0176-4

  日期：2005.11

  Tetrapeptides based on amino acids involved in the catalytic site of RNase T1 were synthesized. These peptides interact with a 96-mer fragment of HIV-1 RNA, which results in phosphodiester bonds splitting. The efficacy of RNA cleavage depends on the mutual arrangement of oppositely charged amino acids (Glu and Arg or Lys) in a peptide. The introduction of an additional cationic fragment (based on bis-quaternary salts of 1,4-diazabicyclooctane) into an RNase mimetic leads to a considerable increase in the efficiency of RNA depolymerization.

  基于RNase T1催化位点氨基酸的四肽已被合成。这些肽与HIV-1 RNA的96-mer片段相互作用，导致磷酸二酯键断裂。RNA切割的效力取决于相反电荷氨基酸（Glu和Arg或Lys）在肽中的相互排列。将附加的阳离子片段（基于1,4-二氮杂双环[4.2.0]辛烷的双季铵盐）引入模拟RNase的结构中，显著提高了RNA解聚的效率。
• Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters
  作者：Federica Prati、Adele Goldman-Pinkovich、Federica Lizzi、Federica Belluti、Roni Koren、Dan Zilberstein、Maria Laura Bolognesi

  DOI：10.1371/journal.pone.0107994

  日期：——

  The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1–15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes) and intracellular (amastigotes) forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 µg/mL and 2.5 µg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively). Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives.

  本研究的目的是探讨通过适当设计的化学探针靶向利什曼原虫转运蛋白的可行性。导致脏器利什曼病的寄生虫利什曼原虫（Leishmania donovani）对精氨酸和赖氨酸呈营养依赖，具有特定的转运蛋白（LdAAP3和LdAAP7）来摄取这些营养物质。探针1-15是通过酰胺连接将细胞毒性醌片段（II和III）与氨基酸（即精氨酸和赖氨酸）结合而制得的。我们研究了合成的结合物对利什曼原虫的细胞外（前鞭毛体）和细胞内（无鞭毛体）形式的毒性，以及它们对相关氨基酸转运蛋白的抑制作用。我们观察到某些结合物确实显示出对寄生虫的毒性；特别是，7被确定为最有效的衍生物（在1 µg/mL和2.5 µg/mL的浓度下，前鞭毛体和无鞭毛体的残留细胞活力分别降至15%和48%）。值得注意的是，6在保留醌II细胞毒活性的同时，对哺乳动物THP1细胞显示无毒性。转运实验表明，新型结合物抑制了赖氨酸、精氨酸和脯氨酸转运蛋白的转运活性。此外，分析结果表明，这些毒性结合物可能通过转运蛋白转位进入细胞。无毒探针通过与天然底物竞争结合转运蛋白而抑制转运，但未被转运。因此，6可能通过利用氨基酸转运蛋白，选择性地将其毒性作用传递至利什曼原虫细胞。这项工作提供了第一个证据，表明人类病原体利什曼原虫的氨基酸转运蛋白可能受到小分子的调节，值得进一步从药物发现和化学生物学的角度进行研究。