methyl α-aminoisobutyryl-α-aminoisobutyrate hydrochloride | 109334-96-5

• 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: methyl α-aminoisobutyryl-α-aminoisobutyrate hydrochloride
• 英文别名: H-Aib-Aib-OMe*HCl；HCl*H-Aib-Aib-OMe；methyl 2-[(2-amino-2-methylpropanoyl)amino]-2-methylpropanoate;hydrochloride
• CAS: 109334-96-5
• 化学式: C₉H₁₈N₂O₃*ClH
• 分子量: 238.714
• InChiKey: GUOYLAZOMOBQLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 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：

  methyl α-aminoisobutyryl-α-aminoisobutyrate hydrochloride 在 palladium on activated charcoal N-甲基吗啉 、 sodium hydroxide 、 ammonium formate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.25h， 生成 N,N-diallyl-O-tert-butyl-L-tyrosyl-α-aminoisobutyryl-α-aminoisobutyric acid
  参考文献：
  名称：

  合成和评估含美法仑的N，N-二亚烷基脑啡肽类似物作为δ阿片受体的不可逆拮抗剂。

  摘要：

  含有苯丙氨酸（Mel）代替Phe4的N，N-二烷基化亮氨酸脑啡肽类似物被合成为δ阿片受体的潜在不可逆拮抗剂。测试了这些化合物以及相应的Phe4肽在GPI和MVD平滑肌制剂中的激动剂和拮抗剂活性。在可逆条件下进行测试时，除两种化合物外，其余八种化合物均在MVD中显示了对microD中的[D-Ala2，D-Leu5]脑啡肽（DADLE）具有拮抗活性；在所有情况下，Mel4肽对DADLE的活性均低于相应的Phe4肽。在较高浓度（10 microM）下，两种活性Mel4类似物（苄基）2Tyr-Gly-Gly-Mel-Leu（2a）和（烯丙基）2Tyr-Aib-Aib-Mel-Leu（3a）均显示弱的不可逆拮抗作用在δ受体上

  DOI：

  10.1021/jm00392a025
• 作为产物：
  描述：

  2-(2-benzyloxycarbonylamino-2-methyl-propionylamino)-2-methylpropionic acid methyl ester 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 0.75h， 以87.2%的产率得到methyl α-aminoisobutyryl-α-aminoisobutyrate hydrochloride
  参考文献：
  名称：

  合成和评估含美法仑的N，N-二亚烷基脑啡肽类似物作为δ阿片受体的不可逆拮抗剂。

  摘要：

  含有苯丙氨酸（Mel）代替Phe4的N，N-二烷基化亮氨酸脑啡肽类似物被合成为δ阿片受体的潜在不可逆拮抗剂。测试了这些化合物以及相应的Phe4肽在GPI和MVD平滑肌制剂中的激动剂和拮抗剂活性。在可逆条件下进行测试时，除两种化合物外，其余八种化合物均在MVD中显示了对microD中的[D-Ala2，D-Leu5]脑啡肽（DADLE）具有拮抗活性；在所有情况下，Mel4肽对DADLE的活性均低于相应的Phe4肽。在较高浓度（10 microM）下，两种活性Mel4类似物（苄基）2Tyr-Gly-Gly-Mel-Leu（2a）和（烯丙基）2Tyr-Aib-Aib-Mel-Leu（3a）均显示弱的不可逆拮抗作用在δ受体上

  DOI：

  10.1021/jm00392a025

文献信息

• Total Synthesis of the α-Helical Eicosapeptide Antibiotic Alamethicin
  作者：Heribert Schmitt、Günther Jung

  DOI：10.1002/jlac.198519850210

  日期：1985.2.12

  identical with the main component F 30 of the microheterogeneous antibiotic metabolite isolated from Trichoderma viride. The antibiotic activities of synthetic alamethicin (1) and the stimulating effect on calcium/calmodulin-dependent guanylate cyclase of Paramecium are identical with those of natural alamethicin. – The uniform synthetic alamethicin (1) shows perfectly homogeneous conductance states of single

  电压依赖性膜成孔多肽抗生素alamethicin F 30（Ac-Aib-Pro-Aib-Ala-Aib-Ala-Gln-Aib-Val-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib- Glu-Gln-Phl，1）是通过链段缩合合成的。使用二环己基碳二亚胺/ 1-羟基苯并三唑和混合酸酐法，可通过链段2-11（4a）和12-20（3a）获得不含外消旋物（<0.8％D组分）的化合物。通过色谱和物理方法（包括13 C NMR，圆二色性和手性气相色谱法）明确表征了中间体。段2–6（5a）和12–20（3）也通过X射线结构确定得到了证明。—在不进行HPLC分离的情况下，获得了非常高的纯度和结晶形式的最终产物1（150 mg）。根据所有分析数据以及通过光谱法和色谱分析法（HPLC，DC）进行的比较，产物1与从木霉属木霉分离的微异质抗生素代谢产物的主要成分F 30相同。合成的alame
• Fungal metabolites. IV. Synthesis of an antibiotic peptide, trichosporin B-V, from Trichoderma polysporum.
  作者：AKira IIDA、Shinya YOSHIMATSU、Masaki SANEKATA、Tetsuro FUJITA

  DOI：10.1248/cpb.38.2997

  日期：——

  The antibiotic icosapeptide trichosporin B-V, which was isolated from Trichoderma polysporum, was synthesized by assembling five peptide fragments via the N,N'-dicyclohexylcarbodiimide method. The synthesized peptide was identical with the natural one.

  从多木霉菌中分离出的抗生素二十碳三肽孢霉菌素BV是通过N，N'-二环己基碳二亚胺法组装五个肽片段而合成的。合成的肽与天然肽相同。
• Fungal Metabolites. IX. Synthesis of a Membrane-Modifying Peptide, Hypelcin A-III, from Hypocrea peltata.
  作者：Kouji MATSUURA、Akgul YESILADA、Akira IIDA、Yasuo NAGAOKA、Yoshihisa TAKAISHI、Tetsuro FUJITA

  DOI：10.1248/cpb.41.1955

  日期：——

  A membrane-modifying peptide antibiotic having uncoupling activity on rat liver mitochondria, hypelcin A-III, has been synthesized by assembling five peptide fragments via the N,N'-dicyclohexylcarbodiimide method. The synthesized hypelcin A-III was identical with the natural product.

  已经通过N，N′-二环己基碳二亚胺方法组装了五个肽片段，合成了对大鼠肝线粒体具有解偶联活性的膜修饰肽抗生素hypelcin A-III。合成的hypelcin A-III与天然产物相同。
• Helix-Inducing α-Aminoisobutyric Acid in Opioid Mimetic Deltorphin C Analogues
  作者：Sharon D. Bryant、Remo Guerrini、Severo Salvadori、Clementina Bianchi、Roberto Tomatis、Martti Attila、Lawrence H. Lazarus

  DOI：10.1021/jm9700530

  日期：1997.8.1

  The achiral symmetric alpha-aminoisobutyric acid (Aib) replaced the critical N-terminal residues of the amphibian skin opioid deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) without detriment to the physicochemical requirements for delta opioid receptor recognition. Substitutions by the alpha,alpha-dialkyl amino acid in place of D-Ala(2) or Phe(3), or both, exhibited high delta receptor affinity (K-i delta = 0.12-3.6 nM) and 5-9-fold greater selectivity (K-i mu/K-i delta = 5000-8500) than the parent compound. This is the first definitive demonstration that the D-chirality of alanine and the aromaticity of phenylalanine are replaceable by an achiral alpha,alpha-dialkylated residue without detrimental effects on ligand binding. Incorporation of the mono-alpha-alkyl amino acid L- or D-Ala at the third position also produced highly selective delta ligands (K-i mu/K-i delta = 2000-3500), albeit with reduced delta affinities (K-i delta = 6-15 nM). Replacement of the anionic residue Asp(4) by Aib yielded an opioid peptide that fit two-site binding models for the delta receptor (eta = 0.763; P < 0.0001) and displayed dual high affinity for both delta and mu receptors, emphasizing the repulsive effect by a negative charge at mu receptor sites and the insignificance of Asp for delta affinity. Molecular dynamics conformational analyses suggested that Aib residues caused distinct changes in deltorphin C secondary structure when substituted for D-Ala(2), Asp(4) and simultaneously D-Ala(2) and Phe(3) but not when substituted for Phe(3). These conformational changes might be critical factors for the proper orientation of reactive constituents of residues in the N-terminal region of deltorphin C. Disparities between binding data and functional bioassays of [Aib(3)] indicated that Phe(3) was required for bioactivity in mouse vas deferens but not for interaction with delta opioid receptors in rat brain membranes.
• IIDA, AKIRA;YOSHIMATSU, SHINYA;SANEKATA, MASAKI;FUJITA, TETSURO, CHEM. AND PHARM. BULL., 38,(1990) N1, C. 2997-3003
  作者：IIDA, AKIRA、YOSHIMATSU, SHINYA、SANEKATA, MASAKI、FUJITA, TETSURO

  DOI：——

  日期：——