N¹,N²,N³,N⁴-tetra(tert-butyloxycarbonyl)spermine | 99560-07-3

• 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: N¹,N²,N³,N⁴-tetra(tert-butyloxycarbonyl)spermine
• 英文别名: N(1),N(5),N(10)-tri-tert-butoxycarbonyl spermine；tetra-N-Boc-spermine；tri-Boc-spermine；N1,N2,N3, N4-tetra-Boc-spermine；tert-butyl N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butyl]carbamate
• CAS: 99560-07-3
• 化学式: C₃₀H₅₈N₄O₈
• 分子量: 602.813
• InChiKey: VQUCJBRWLAGLCA-UHFFFAOYSA-N

物化性质

• 沸点：
  671.2±55.0 °C(Predicted)
• 密度：
  1.057±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  42
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-溴丙烯 、 N¹,N²,N³,N⁴-tetra(tert-butyloxycarbonyl)spermine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 C₃₆H₆₆N₄O₈
  参考文献：
  名称：

  在溶液中通过共价自组装形成独立的、单单体厚的二维聚合物

  摘要：

  二维 (2D) 聚合物的设计和合成是一项具有挑战性的任务，迄今为止，只能通过固体表面“模板”或在二维密闭空间中预先组织构建块的帮助才能在解决方案中实现。我们提出了一种在溶液中合成独立的、共价键合的、单单体厚度的二维聚合物的新方法，通过采用刚性、盘状结构的形状导向共价自组装，在固体表面或界面上没有任何结构单元的预组织在其外围具有侧向易反应基团的块。我们通过 (烯丙氧基)12CB[6]、具有 12 个侧向易反应性烯烃基团的葫芦 [6] 脲 (CB[6]) 衍生物和 1 之间的硫醇-烯“点击”反应证明了我们的策略，2-乙二硫醇合成坚固且易于转移的二维聚合物。我们可以利用完全质子化精胺（两端带正电荷）与 CB[6] 的高结合亲和力，在合成过程中通过静电排斥使每个单独的聚合物片彼此分开，有史以来第一次获得，溶液中的单一单体厚度的二维聚合物。CB[6] 重复单元在所得二维聚合物中的排列已使用金纳米颗粒

  DOI：

  10.1021/ja4002019
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 氨 、 氢气 作用下， 以 乙醇 为溶剂， 反应 54.0h， 生成 N¹,N²,N³,N⁴-tetra(tert-butyloxycarbonyl)spermine
  参考文献：
  名称：

  Mild and Efficient Synthesis of N ¹,N ⁵,N ¹⁰-Tri-tert-butoxycarbonyl Spermine

  摘要：

  This article describes a mild and efficient synthesis of N-1,N-5,N-10-tri-tert-butoxycarbonyl spermine from putrescine, with a 41% overall yield. The key steps include a Michael addition and Raney nickel (W-2) reduction. The advantages of this synthesis include a simple procedure, mild conditions, and good yields.

  DOI：

  10.1080/00397911.2010.523856

文献信息

• A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues
  作者：P Wellendorph

  DOI：10.1016/s0223-5234(02)00003-x

  日期：2003.1

  analogues, a pharmacologically important class of polyamine conjugates, is described. The solution-phase procedure is illustrated by gram-scale synthesis of philanthotoxins PhTX-343 and PhTX-12. Selectively protected polyamines are coupled to N(alpha)-Fmoc-protected amino acid pentafluorophenyl esters. After removal of the N(alpha)-Fmoc group, the amine is coupled with carboxylic acid pentafluorophenyl

  描述了用于快速合成费洛托辛类似物（药理上重要的一类多胺缀合物）的通用改进方法。溶液阶段的过程通过嗜氧性毒素PhTX-343和PhTX-12的克规模合成得到说明。选择性保护的多胺与Nα-Fmoc保护的氨基酸五氟苯基酯偶联。除去Nα-Fmoc基团后，将胺与羧酸五氟苯基酯偶联。脱保护，然后通过在十八烷基甲硅烷基二氧化硅上的真空液相色谱法（RP-18相）快速有效地纯化，以总产率的74-78％得到了费洛托辛类似物。
• The Effects of Conformational Constraints and Steric Bulk in the Amino Acid Moiety of Philanthotoxins on AMPAR Antagonism
  作者：Malene R. Jørgensen、Christian A. Olsen、Ian R. Mellor、Peter N. R. Usherwood、Matthias Witt、Henrik Franzyk、Jerzy W. Jaroszewski

  DOI：10.1021/jm049906w

  日期：2005.1.1

  at ionotropic receptors (e.g., AChR or iGluR). To determine possible effects of variations of the amino acid side chain, a library consisting of seventeen PhTX-343 analogues was prepared. Thus, tyrosine was replaced by either apolar, conformationally constrained, or bulky amino acids, whereas the acyl unit and the polyamine moiety were kept unchanged. Analogues with tertiary amide groups were prepared

  Philanthotoxin-343（PhTX-343）是黄蜂毒素PhTX-433的合成类似物，是离子型受体（例如AChR或iGluR）的非竞争性拮抗剂。为了确定氨基酸侧链变异的可能影响，制备了由17种PhTX-343类似物组成的文库。因此，酪氨酸被非极性，构象受限或庞大的氨基酸取代，而酰基单元和多胺部分保持不变。首次制备了具有叔酰胺基团的类似物。将五氟苯基酯用于酰胺键的形成，建立了费洛托辛溶液和固相合成的通用方案（总收率分别为39-90％和42-54％）。测试了这些类似物拮抗海藻酸盐诱导的爪蟾卵母细胞表达的大鼠脑mRNA的2-氨基-3-（3-羟基-5-甲基-4-异恶唑酰基）丙酸受体（AMPAR）的海因酸盐诱导电流的能力。这表明氨基酸部分中的空间体积被很好地耐受，并且表明与AMPAR的结合不涉及作为氢键供体的α-NHCO基团。
• Structure–activity relationships of lipopolysaccharide sequestration in guanylhydrazone-bearing lipopolyamines
  作者：Wenyan Wu、Diptesh Sil、Michal L. Szostak、Subbalakshmi S. Malladi、Hemamali J. Warshakoon、Matthew R. Kimbrell、Jens R. Cromer、Sunil A. David

  DOI：10.1016/j.bmc.2008.11.051

  日期：2009.1

  The toxicity of Gram-negative bacterial endotoxin (lipopolysaccharide, LPS) resides in its structurally highly conserved glycolipid component called lipid A. Our major goal has been to develop small-molecules that would sequester LPS by binding to the lipid A moiety, so that it could be useful for the prophylaxis or adjunctive therapy of Gram-negative sepsis. We had previously identified in rapid-throughput screens several guanylhydrazones as potent LPS binders. We were desirous of examining if the presence of the guanylhydrazone (rather than an amine) functionality would afford greater LPS sequestration potency. In evaluating a congeneric set of guanylhydrazone analogues, we find that C-16 alkyl substitution is optimal in the N-alkylguanylhydrazone series; a homospermine analogue with the terminal amine N-alkylated with a C-16 chain with the other terminus of the molecule bearing an unsubstituted guanylhydrazone moiety is marginally more active, suggesting very slight, if any, steric effects. Neither C-16 analogue is significantly more active, than the N-C-16-alkyl or N-C-16-acyl compounds that we had characterized earlier, indicating that basicity of the phosphate-recognizing cationic group, is not a determinant of LPS sequestration activity. (C) 2008 Elsevier Ltd. All rights reserved.
• Lysine–spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants
  作者：Mark R. Burns、Stewart J. Wood、Kelly A. Miller、Thuan Nguyen、Jens R. Cromer、Sunil A. David

  DOI：10.1016/j.bmc.2005.01.038

  日期：2005.4

  Lipopolysaccharides (LPS), otherwise termed `endotoxins' are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of `Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. (c) 2005 Elsevier Ltd. All rights reserved.
• Chemistry of naturally occurring polyamines. 9. Synthesis of spermidine and spermine photoaffinity labeling reagents
  作者：Srinivasan Nagarajan、Bruce Ganem

  DOI：10.1021/jo00350a059

  日期：1985.12