1,12-dodecano-bis(L-Phe) | 182684-42-0

• 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: 1,12-dodecano-bis(L-Phe)
• 英文别名: (2S)-2-amino-N-[12-[[(2S)-2-amino-3-phenylpropanoyl]amino]dodecyl]-3-phenylpropanamide
• CAS: 182684-42-0
• 化学式: C₃₀H₄₆N₄O₂
• 分子量: 494.721
• InChiKey: SDTMQKDEKXSQIW-NSOVKSMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,12-dodecano-bis(L-Phe) 在 TEA 、 焦碳酸二乙酯 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,12-dodecano-bis(L-Phe-L-Val-L-LeuBoc)
  参考文献：
  名称：

  与-Phe-Phe-和-Phe-Phe-X序列缀合的新型迷你平行双链肽的合成，构象和化学性质。

  摘要：

  为了研究与阿尔茨海默氏病相关的β-淀粉样肽中所含的-Phe-Phe-Val-或-Phe-Phe-序列的化学构象和功能，这是一系列与两个肽残基缀合在一起的微型平行双链肽设计并准备了垫片。通过圆二色性（CD）光谱和NMR二维（2D）核Overhauser增强和交换光谱（NOESY）测量来阐明化合物的结构。1,2-乙醇双（L-Phe-L-Phe-L-Leu），1,12-十二烷双（L-Phe-L-Phe-L-Leu），1,12-十二烷的结构-bis（L-Phe-L-Phe-L-Val）和1,12-十二烷（D-Phe-D-Phe-D-Leu）与L-Leu和L-Val残基缀合显示β角形核。二面角（θ= +75度，ω= +180度，phi = +90度，phi = -87度，从实验耦合常数（J）数据等获得的psi = +180度）支持1,12-十二烷双（L-Phe-L-Phe）采用β-转角模拟成核。1,

  DOI：

  10.1248/cpb.48.920
• 作为产物：
  描述：

  1,12-二氨基十二烷 在 palladium on activated charcoal 氢气 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 1,12-dodecano-bis(L-Phe)
  参考文献：
  名称：

  与-Phe-Phe-和-Phe-Phe-X序列缀合的新型迷你平行双链肽的合成，构象和化学性质。

  摘要：

  为了研究与阿尔茨海默氏病相关的β-淀粉样肽中所含的-Phe-Phe-Val-或-Phe-Phe-序列的化学构象和功能，这是一系列与两个肽残基缀合在一起的微型平行双链肽设计并准备了垫片。通过圆二色性（CD）光谱和NMR二维（2D）核Overhauser增强和交换光谱（NOESY）测量来阐明化合物的结构。1,2-乙醇双（L-Phe-L-Phe-L-Leu），1,12-十二烷双（L-Phe-L-Phe-L-Leu），1,12-十二烷的结构-bis（L-Phe-L-Phe-L-Val）和1,12-十二烷（D-Phe-D-Phe-D-Leu）与L-Leu和L-Val残基缀合显示β角形核。二面角（θ= +75度，ω= +180度，phi = +90度，phi = -87度，从实验耦合常数（J）数据等获得的psi = +180度）支持1,12-十二烷双（L-Phe-L-Phe）采用β-转角模拟成核。1,

  DOI：

  10.1248/cpb.48.920

文献信息

• Refining hydrogelator design: soft materials with improved gelation ability, biocompatibility and matrix for in situ synthesis of specific shaped GNP
  作者：Dibyendu Das、Subhabrata Maiti、Sayanti Brahmachari、Prasanta Kumar Das

  DOI：10.1039/c1sm05608e

  日期：——

  Despite the continuous surge in the development of new supramolecular gels, the prediction of a gelator's structure still remains elusive. It is also imperative to consolidate the existing inventory of gelators and devise ways to make the gels functional. In the present work, L-phenylalanine based poor (C-16) or non-gelating (C-12 tail) amphiphiles were converted to excellent gelators with the simple incorporation of N-terminal protected amino acid/dipeptide at the end of the alkyl tail. More than 6-fold enhancement in gelation efficiency was observed for amino acid/dipeptides incorporated at the tail of amphiphile in comparison to the corresponding unmodified alkyl tail. Interestingly, amphiphile with the tertiary butyloxycarbonyl (Boc) protected amino acid at the tail had better gelation ability than the amphiphile with the aromatic Fmoc (N-fluorenyl-9-methoxycarbonyl) protecting group. Spectroscopic investigations (XRD and FTIR) revealed that the modification at the tail compels the amphiphiles to take a different course of self-assembly than that adopted by their predecessors (alkyl tailed gelator, C-16). For example, in the case of the amphiphile having a dipeptide at the tail, formation of β-sheet structure through anti-parallel arrangement between the molecules results in notable improvement in its gelation ability. Most importantly, these tail modified amphiphiles were capable of in situ synthesis of gold nanoparticles (GNPs) of specific shape without the help of any external reducing agents in the newly developed soft materials. The biocompatibility of hydrogels is also crucial for their prolific biomedicinal functions. MTT assay showed dramatic improvement in the biocompatibility of the tail modified hydrogelators towards mammalian cells in comparison to the amphiphiles having no amino acid at the tail.

  尽管新型超分子凝胶的发展持续激增，但凝胶剂结构的预测仍然难以捉摸。同样迫切的是整合现有凝胶剂清单，并设计方法使凝胶具有功能性。在本研究中，基于L-苯丙氨酸的不良（C-16）或非凝胶化（C-12尾部）的两性分子，通过简单地在烷基尾部末端引入N端保护的氨基酸/二肽，转化为优秀的凝胶剂。与未修饰的相应烷基尾部相比，在两性分子尾部引入氨基酸/二肽后，凝胶化效率提高了6倍以上。有趣的是，尾部带有叔丁氧羰基（Boc）保护氨基酸的两性分子比尾部带有芳香性Fmoc（N-芴基-9-甲氧羰基）保护基的两性分子具有更好的凝胶化能力。光谱学研究（XRD和FTIR）揭示，尾部的修饰迫使两性分子采取与前身（烷基尾部凝胶剂，C-16）不同的自组装途径。例如，在尾部具有二肽的两性分子中，通过分子间的反平行排列形成β-折叠结构，显著改善了其凝胶化能力。最重要的是，这些尾部修饰的两性分子能够在新型软材料中，无需任何外部还原剂的帮助，实现特定形状金纳米颗粒（GNPs）的原位合成。水凝胶的生物相容性对其丰富的生物医学功能也至关重要。MTT assay显示，与尾部没有氨基酸的两性分子相比，尾部修饰的水凝胶剂对哺乳动物细胞的生物相容性有了显著提高。
• Exceptional adhesive and gelling properties of fibrous nanoscopic tapes of self-assembled bipolar urethane amides of L-phenylalanine
  作者：Santanu Bhattacharya、S. N. Ghanashyam Acharya、A. R. Raju

  DOI：10.1039/cc9960002101

  日期：——

  Seven L-phenylalanine based alkyl (monopolar) and alkanediyl (bipolar) derivatives are synthesized; while the bipolar urethane amides form gels and show strong adhesive properties, the monopolar analogues form fibrous nanoscopic cloth-like tapes.

  合成了七种基于L-苯丙氨酸的烷基（单极性）和烷二基（双极性）衍生物；而双极性氨基甲酸酯酰胺形成凝胶并显示出强烈的粘附性，单极性类似物则形成纤维状的纳米级布状带。
• Diastereomer-Specific Effects of Double-Stranded Peptides Conjugated with -L-Tyr-L-Phe- or -L-Tyr-D-Phe- Residues on Tyrosine Phosphorylation and Inhibition of srctsNRK, A431, MCF-7, and DU145 Cell Growth
  作者：Shigeki Kobayashi、Nahomi Atuchi、Hidetaka Wakamatsu、Mayuko Hattori、Ayumi Kawada、Kouji Asano

  DOI：10.1248/cpb.55.1585

  日期：——

  The interaction between growth inhibition and chirality, especially of diastereomers, has an important modifying effect on cancer cell proliferation. Previously, we have reported on the design, synthesis, and chemical properties of a series of novel, double-stranded peptides, (y-AA–x-AA)2-(CH2)12, with –y-AA–x-AA– and –z-AA–y-AA–x-AA– sequences conjugated to the spacer. Here, we extend those results by showing that (D-, L-) and (L-, D-) diastereomers are more potent inhibitors of tyrosine phosphorylation than (L-, L-). Although the replacement of the L-Phe–L-Phe sequence with L-Tyr–L-Phe produces a less active inhibitor, the double-stranded peptide conjugated with L-Tyr–D-Phe is more active than that conjugated with L-Tyr–L-Phe. In addition, we show that SDS-PAGE gel profiles of tyrosine phosphorylation following treatment with bis(y-Tyr–x-Phe)-N,N-dodecane-1,12-diamine appear very similar to profiles of tyrosine phosphorylation following treatment with an analog of the tyrosine kinase inhibitor, erbstatin. Moreover, the level of autophosphorylation of the epidermal growth factor receptor kinase domain (EGFRKD) treated with bis(L-Tyr–D-Phe)-N,N-dodecane-1,12-diamine was lower than that seen following treatment with bis(L-Phe–D-Phe)-N,N-dodecane-1,12-diamine. These data provide new insights for the control of cancer cell proliferation through drug designs which replace the less active –L-Phe–L-Phe– (and –D-Phe–L-Phe–) with the more active –L-Tyr–L-Phe- (and –L-Tyr–D-Phe–) sequence.

  生长抑制与手性之间的相互作用，特别是对映异构体的相互作用，对癌细胞增殖具有重要的修饰效应。此前，我们报告了一系列新颖的双链肽（y-AA–x-AA）₂-(CH₂)₁₂的设计、合成和化学性质，其中包含与间隔连接的–y-AA–x-AA–和–z-AA–y-AA–x-AA–序列。在这里，我们扩展了这些结果，表明（D-，L-）和（L-，D-）对映异构体在酪氨酸磷酸化的抑制效果上比（L-，L-）更强。尽管用L-Tyr–L-Phe序列替换L-Phe–L-Phe序列会产生活性较低的抑制剂，但与L-Tyr–D-Phe连接的双链肽的活性高于与L-Tyr–L-Phe连接的那种。此外，我们显示了处理过双（y-Tyr–x-Phe）-N,N-十二烷-1,12-二胺后的酪氨酸磷酸化的SDS-PAGE凝胶谱与酪氨酸激酶抑制剂erbstatin的类似物处理后的磷酸化谱非常相似。此外，处理过双（L-Tyr–D-Phe）-N,N-十二烷-1,12-二胺的表皮生长因子受体激酶域（EGFRKD）的自磷酸化水平低于处理过双（L-Phe–D-Phe）-N,N-十二烷-1,12-二胺的情况。这些数据为通过药物设计控制癌细胞增殖提供了新视角，药物设计用更具活性的–L-Tyr–L-Phe–（及–L-Tyr–D-Phe–）序列替代活性较低的–L-Phe–L-Phe–（及–D-Phe–L-Phe–）序列。
• SYNTHESIS OF DIAMIDO GELLANTS BY USING DANE SALTS OF AMINO ACIDS
  申请人：EVONIK INDUSTRIES AG

  公开号：US20150073172A1

  公开（公告）日：2015-03-12

  The invention relates to a method for the synthesis of a compound according to formula I comprising the following steps: a) reacting a Dane salt according to formula II and a Dane salt according to formula III with a coupling reagent; b) adding a diamine according to formula IV to the reaction mixture; and c) adding an acid to the reaction mixture to adjust the pH value of the reaction to <7; wherein L represents a C 2 -C 20 alkyl group, a C 6 -C 20 aryl group, or a C 7 -C 20 alkylaryl group; R 1 and R 2 can be identical or different and represent a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 hydroxyalkyl group, a C 1 -C 4 thioether group, a C 6 -C 20 aryl group, a C 7 -C 26 ) alkylaryl group, a C 7 -C 20 alkylhydroxyaryl group, a C 4 -C 20 alkylheteroaryl group with 1 to 4 heteroatoms; or a C 1 -C 4 alkylcarboxylic moiety, which may be an acid, an amide, or which may be esterified with a C 1 -C 6 alkyl group or a C 7 -C 20 alkylaryl group; R 3 represents a C 1 -C 4 alkyl group; R 4 represents a hydrogen atom, or a C 1 -C 4 alkyl group; R 5 represents a C 1 -C 4 alkyl group; and X represents an alkali metal.

  本发明涉及一种合成配方I化合物的方法，包括以下步骤：a）用偶联试剂反应式II和式III的Dane盐；b）向反应混合物中加入式IV的二胺；c）向反应混合物中加入酸，以调节反应的pH值小于7；其中L代表C2-C20烷基、C6-C20芳基或C7-C20烷基芳基；R1和R2可以相同也可以不同，代表氢原子、C1-C4烷基、C1-C4羟基烷基、C1-C4硫醚基、C6-C20芳基、C7-C26烷基芳基、C7-C20烷基羟基芳基、具有1至4个杂原子的C4-C20烷基杂芳基或C1-C4烷基羧酸基，可以是酸、酰胺或酯化为C1-C6烷基或C7-C20烷基芳基；R3代表C1-C4烷基；R4代表氢原子或C1-C4烷基；R5代表C1-C4烷基；X代表碱金属。
• SYNTHESIS OF DIAMIDO GELLANTS BY USING AMINO ACID N-CARBOXYANHYDRIDES
  申请人：Bindl Martin

  公开号：US20150175527A1

  公开（公告）日：2015-06-25

  The invention relates to a method for the synthesis of a compound according to formula I comprising the following steps: a) reacting a N-carboxyanhydride according to formula II and a N-carboxy-anhydride according to formula III with a diamine according to formula IV and b) adding an acid to the reaction to adjust the pH value of the reaction to <7; wherein L represents a C 2 -C 20 alkyl group, a C 6 -C 20 aryl group, or a C 7 -C 20 alkylaryl group; and R 1 and R 2 can be identical or different and represent a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 hydroxyalkyl group, a C 1 -C 4 thioether group, a C 6 -C 20 aryl group, a C 7 -C 20 alkylaryl group, a C 7 -C 20 alkylhydroxyaryl group, a C 4 -C 20 alkylheteroaryl group with 1 to 4 heteroatoms; or a C 1 -C 4 alkylcarboxylic moiety, which may be an acid, an amide, or which may be esterified with a C 1 -C 6 alkyl group or a C 7 -C 20 alkylaryl group.