H-Leu-Ala-OMe*HCl

• 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: H-Leu-Ala-OMe*HCl
• 英文别名: L-leucinyl-alanine methyl ester hydrochloride；L-leucinyl-L-alanine methyl ester hydrochloride；Leu-Ala-OMe*HCl；leucylalaninmethylesterhydrochloride；Leucylalaninmethylesterhydrochlorid (germ.)；leucylalanine methylester hydrochloride；methyl (2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]propanoate;hydrochloride
• 化学式: C₁₀H₂₀N₂O₃*ClH
• 分子量: 252.741
• InChiKey: SVXOYJTTZKTWRN-WSZWBAFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.46
• 重原子数：
  16.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  H-Leu-Ala-OMe*HCl 在 dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer 、 silver(I) acetate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 silver(l) oxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.5h， 生成 (6S,9S,12S)-methyl 6-((2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1-(pyridin-2-yl)-1H-indol-3-yl)methyl)-9-isobutyl-2,2,12-trimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate
  参考文献：
  名称：

  Rhodium(III)-Catalyzed C–H Alkenylation: Access to Maleimide-Decorated Tryptophan and Tryptophan-Containing Peptides

  摘要：

  Maleimide is widely applied in many fields, especially in antibody-drug conjugations and peptide drugs. Herein, we develop a strategy for the C-H alkenylation of tryptophan and tryptophan-containing peptides, providing a synthetic route of decorating maleimide on peptides. The method has a high tolerance of functional groups and protecting groups. Furthermore, this method was applied to prepare peptide conjugation with molecules such as drugs and fluorescence probes. Moreover, macrocyclic peptides were obtained via this reaction.

  DOI：

  10.1021/acs.orglett.0c00086
• 作为产物：
  描述：

  L-亮氨酸乙酯 在 palladium on activated charcoal N-甲基吗啉 、 2,6-二甲基吡啶 、 盐酸 、 sodium hydroxide 、 氢气 、 N,N,N,N-tetraethylammonium tetrafluoroborate 、 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 为溶剂， 反应 17.0h， 生成 H-Leu-Ala-OMe*HCl
  参考文献：
  名称：

  肽与N- Phd保护基合成人淋巴母细胞干扰素疏水片段14-20 L-Ala-Leu-Ile-Leu-Leu-Ala-Gln的合成†

  摘要：

  氨基酸酯以59–97％的产率转化为N-（3,5-二叔丁基-4-氧代-1-苯基-2,5-环己二烯基）氨基酸酯（N -PChd氨基酸酯）8经由在2,6-存在阳极氧化二-叔丁基-4-苯基苯酚（1A）。水解8导致相应的N -PChd氨基酸9。新型的PChd保护基对碱性试剂稳定，可以通过氢化或酸解去除，并且对寡肽在有机溶剂中表现出良好的增溶性能。ñ-PChd氨基酸无需消旋就可以偶联，它们易于制备和存储，并且易于结晶。-使用常规的肽合成方法和在二氯甲烷中或在催化氢化中用10–50％三氟乙酸进行PChd脱保护的方法，制备了七肽HuIFN-α（Ly）14–20 L-Ala-Leu-Ile-Leu-Leu-Ala-Gln。如柱色谱和薄层色谱法，13 C-NMR光谱法，手性气相色谱法和常用分析方法所示，合成得到的收率和纯度均很高。

  DOI：

  10.1002/jlac.198219820608

文献信息

• Highly Stereoselective Synthesis of Natural-Product-Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence
  作者：Radell Echemendía、Alexander F. de La Torre、Julia L. Monteiro、Michel Pila、Arlene G. Corrêa、Bernhard Westermann、Daniel G. Rivera、Márcio W. Paixão

  DOI：10.1002/anie.201412074

  日期：2015.6.22

  In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including

  为了提供一种通往天然产物杂种的有效途径，本文描述了一种高效，高度立体选择性的单锅法，该方法包括将1,3-二羰基加至α，β-不饱和醛的有机催化共轭加成反应，然后进行分子内异氰酸酯加成反应。基于多组分的反应。这种方法能够快速组装复杂的天然产物杂种，包括多达四个不同的分子片段，例如氢喹啉酮，色烯，哌啶，肽，脂质和糖苷部分。该策略将有机催化的立体控制与多组分反应产生多样性的特征相结合，从而导致结构独特的拟肽药物整合了杂环，脂质和糖部分。
• Fluorescent Peptides Labeled with Environment-Sensitive 7-Aminocoumarins and Their Interactions with Lipid Bilayer Membranes and Living Cells
  作者：Tokiko Murase、Toshitada Yoshihara、Keiichi Yamada、Seiji Tobita

  DOI：10.1246/bcsj.20120314

  日期：2013.4.15

  The photophysical properties of protected nonnatural amino acids Boc–l-Dap(7DEAC)–OMe (7DEAC: 7-diethylaminocoumarin) and Boc–l-Dap(C343)–OMe (C343: coumarin 343) were investigated to evaluate the suitability of these amino acids as fluorescent units in peptide-based fluorescent biosensors. The absorption and fluorescence spectra of Boc–l-Dap(7DEAC)–OMe and Boc–l-Dap(C343)–OMe exhibited significant red shifts with increasing solvent polarity. The fluorescence quantum yield and lifetime of Boc–l-Dap(7DEAC)–OMe solutions decreased remarkably with increasing solvent polarity, whereas those of Boc–l-Dap(C343)–OMe were slightly affected by the solvent polarity. Fluorescent peptides H–Dap(7DEAC)–LLA–OMe (1), H–Dap(7DEAC)–KLA–OMe (2), and H–Dap(7DEAC)–ELA–OMe (3) labeled with environment-sensitive 7DEAC were synthesized to examine the interactions of these labeled peptides with lipid membranes and living cells. Neutral 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and anionic 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG) liposomes were used to investigate peptide–membrane interactions. Hydrophobic peptide 1 exhibited high affinities to both DMPC and DMPC/DMPG mixed membranes. Of the three peptides, cationic peptide 2 exhibited the strongest affinity to DMPC/DMPG membranes, whereas anionic peptide 3 showed a much lower affinity to DMPC/DMPG membranes. These results could be interpreted based on hydrophobic and electrostatic interactions between the peptides and membranes. Peptide 1 was efficiently internalized into HeLa cells, whereas peptides 2 and 3 showed a much lower intracellular delivery.

  研究了受保护的非天然氨基酸Boc–l-Dap(7DEAC)–OMe (7DEAC: 7-二乙基氨基香豆素)和Boc–l-Dap(C343)–OMe (C343: 香豆素343)的光物理性质,以评估这些氨基酸作为肽基荧光生物传感器的荧光单元的适用性。Boc–l-Dap(7DEAC)–OMe和Boc–l-Dap(C343)–OMe的吸收和荧光光谱随着溶剂极性的增加呈现出显著的红移。Boc–l-Dap(7DEAC)–OMe溶液的荧光量子产率和寿命随着溶剂极性的增加显著降低,而Boc–l-Dap(C343)–OMe的荧光量子产率和寿命受溶剂极性的影响较小。合成了标记有环境敏感的7DEAC的荧光肽H–Dap(7DEAC)–LLA–OMe (1)、H–Dap(7DEAC)–KLA–OMe (2)和H–Dap(7DEAC)–ELA–OMe (3),以检查这些标记肽与脂质膜和活细胞的相互作用。使用中性的1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱(DMPC)和阴离子的1,2-二肉豆蔻酰-sn-甘油-3-[磷酸-rac-(1-甘油)] (DMPG)脂质体来研究肽-膜相互作用。疏水性肽1对DMPC和DMPC/DMPG混合膜表现出高亲和力。在这三种肽中,阳离子肽2对DMPC/DMPG膜表现出最强的亲和力,而阴离子肽3对DMPC/DMPG膜的亲和力要低得多。这些结果可以根据肽和膜之间的疏水性和静电相互作用来解释。肽1被有效地内化到HeLa细胞中,而肽2和3的细胞内递送要低得多。
• Design and Synthesis of Potent, Selective Inhibitors of Endothelin-Converting Enzyme
  作者：Eli M. Wallace、John A. Moliterni、Michael A. Moskal、Alan D. Neubert、Nicholas Marcopulos、Lisa B. Stamford、Angelo J. Trapani、Paula Savage、Mary Chou、Arco Y. Jeng

  DOI：10.1021/jm970787c

  日期：1998.4.1

  ECE-1 and NEP with IC50 values of 14 nM and 2 microM, respectively. Similarly, (S)-[[1-[(2-biphenyl-4-ylethyl)carbamoyl]-4-(2-fluorophenyl)but-3- yny l]amino]methyl]phosphonic acid (56), an arylacetylene amino phosphonate amide, had IC50's of 33 nM and 6.5 microM for ECE-1 and NEP, respectively. Slight modification of the aryl moiety was found to have dramatic effects on ECE-1/NEP selectivity. The 2-fluoro

  内皮素-1是迄今为止发现的最有效的肽血管收缩剂。该肽的翻译后加工的最后一步是内皮素转化酶-1（ECE-1）对其前体的转化，该酶是一种金属蛋白酶，与中性内肽酶24.11（NEP）表现出很高的氨基酸序列同一性，尤其是在催化中心。已经制备了一系列有效的和选择性的含芳基乙炔的ECE-1抑制剂。（S，S）-3-环己基-2-[[5-（2,4-二氟苯基）-2-[（膦酰基甲基）氨基]戊-4-炔基]氨基]丙酸（47），芳基乙炔基氨基发现膦酸二肽可抑制ECE-1和NEP，IC50值分别为14 nM和2 microM。类似地，（S）-[[[[[1-[（2-联苯-4-基乙基）氨基甲酰基] -4-（2-氟苯基）丁-3-yny]氨基]甲基]膦酸（56），芳基乙炔氨基膦酸酯酰胺，对ECE-1和NEP的IC50分别为33 nM和6.5 microM。发现芳基部分的轻微修饰对ECE-1 / NEP选择性具有显着影响。2-氟
• Modification of constrained peptides by ring-closing metathesis reaction
  作者：Sambasivarao Kotha、Nampally Sreenivasachary、Kumar Mohanraja、Susheel Durani

  DOI：10.1016/s0960-894x(01)00227-x

  日期：2001.6

  Ring-closing metathesis (RCM) with alpha,alpha-diallylglycyl peptides is shown to furnish alpha,alpha-cyclopentenylglycyl peptides as conformationally restrained analogues in the form of post-translational type peptide modification suitable for both peptidomimetic and combinatorial chemistry applications.

  显示具有α，α-二烯丙基糖基肽的闭环复分解（RCM）以适合于拟肽和组合化学应用的翻译后类型肽修饰的形式提供α，α-环戊烯基糖基肽作为构象受限的类似物。
• Metallkomplexe mit biologisch wichtigen Liganden, CLXI [1]. Halbsandwich-Komplexe mit tert-Leucin, Dipeptiden, Pentaglycin und Glutathion als Liganden / Metal Complexes with Biologically Important Ligands, CLXI [1]. Halfsandwich Complexes with tert-Leucine, Dipeptides, Pentaglycine and Glutathione
  作者：Winfried Hoffmüller、Harald Dialer、Wolfgang Beck

  DOI：10.1515/znb-2005-1211

  日期：2005.12.1

  Reactions of L-tert-Leucine (tert-butylglycine), tert-leucine methyl ester, GlyValOMe, and Leu- AlaOMe with the chloro-bridged complexes [Cp*IrCl₂]₂, [(p-cymene)RuCl₂]₂ or [(C₆Me₆)RuCl₂]₂ in the presence of NaOMe give the complexes [Cp*Ir(Cl)NH₂CH(R)CO₂] (1), [(p-cymene)Ru(Cl)- NH₂CH(R)CO₂] (2), Cp*Ir(Cl₂)[NH₂CH(R)CO₂Me] (5), (C₆Me₆)Ru(Cl)[NH₂CH₂CONHCH(R)- CO₂Me]}⁺Cl⁻ (6), [Cp*Ir(Cl)NH₂CH₂CONCH(R)CO₂Me] (7), [Cp*Ir(Cl)NH₂CH(CH₂CHMe₂)- CONCH(R)CO₂Me)] (8), and Cp*Ir(Cl₂)[NH₂CH₂CONHCH(R)CO₂Me) (9).

  With pentaglycine the complexes [Cp*Ir(Cl₂)(pentaglycinate⁺Na⁺)] (10) and [(C₆Me₆)Ru(pentaglycineOMe- H⁺)] (11) could be isolated. Coordination of one equivalent of the S-protected tripeptide glutathione to [Cp*Ir(Cl)] and to [(C₆Me₆)Ru(Cl)] was observed. Some in situ prepared (p-cymene)Ru complexes with deprotonated dipeptide esters were tested as catalysts and the complex [(p-cymene)Ru(Cl)(NH₂CH(CHMeEt)NCH (CHMe₂)CO₂tert-Bu)] gave a yield of 73% and moderate entantiomeric excess (36% ee) in the transfer hydrogenation of acetophenone to 2-propanol.

  L-叔-亮氨酸（叔丁基甘氨酸）、叔亮氨酸甲酯、GlyValOMe 和 Leu-AlaOMe 与氯桥联配合物 [Cp*IrCl₂]₂、[(p-环己烯)RuCl₂]₂ 或 [(C₆Me₆)RuCl₂]₂ 在 NaOMe 存在下反应，得到配合物 [Cp*Ir(Cl)NH₂CH(R)CO₂] (1)、[(p-环己烯)Ru(Cl)- NH₂CH(R)CO₂] (2)、Cp*Ir(Cl₂)[NH₂CH(R)CO₂Me] (5)、(C₆Me₆)Ru(Cl)[NH₂CH₂CONHCH(R)CO₂Me]}⁺Cl⁻ (6)、[Cp*Ir(Cl)NH₂CH₂CONCH(R)CO₂Me] (7)、[Cp*Ir(Cl)NH₂CH(CH₂CHMe₂)- CONCH(R)CO₂Me)] (8) 和 Cp*Ir(Cl₂)[NH₂CH₂CONHCH(R)CO₂Me) (9)。

  与五甘氨酸配合物 [Cp*Ir(Cl₂)(五甘氨酸盐⁺Na⁺)] (10) 和 [(C₆Me₆)Ru(五甘氨酸甲酯- H⁺)] (11) 可以被分离。观察到一等量 S-保护的三肽谷胱甘肽与 [Cp*Ir(Cl)] 和 [(C₆Me₆)Ru(Cl)] 的配位。一些原位制备的 (p-环己烯)Ru 配合物与去质子化的二肽酯作为催化剂，复合物 [(p-环己烯)Ru(Cl)(NH₂CH(CHMeEt)NCH (CHMe₂)CO₂叔丁基)] 在苯乙酮转移氢化为异丙醇中产率为73%，对映选择性中等（36% ee）。