alpha,alpha-二甲基-3,5-二甲氧基苄基-苯丙氨酸 | 39508-07-1

• 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
• 中文名称: alpha,alpha-二甲基-3,5-二甲氧基苄基-苯丙氨酸
• 中文别名: DDZ-L-苯丙氨酸
• 英文名称: Ddz-L-Phe-OH
• 英文别名: Ddz-Phe-OH；(2S)-2-[2-(3,5-dimethoxyphenyl)propan-2-yloxycarbonylamino]-3-phenylpropanoic acid
• CAS: 39508-07-1
• 化学式: C₂₁H₂₅NO₆
• 分子量: 387.433
• InChiKey: MRRFBTOYJLDDTC-SFHVURJKSA-N

物化性质

• 沸点：
  575.5±50.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  、 alpha,alpha-二甲基-3,5-二甲氧基苄基-苯丙氨酸 在 N-甲基吡咯烷酮 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成
  参考文献：
  名称：

  大环拟肽的高效并行合成。

  摘要：

  报道了一种化学和构象多样的大环拟肽的固相平行合成的新方法。该方法的关键特征是获得广泛的化学和构象多样性。报道了有关大环化步骤的合成和机理研究。

  DOI：

  10.1016/j.bmcl.2008.06.085
• 作为产物：
  描述：

  3,5-二甲氧基-α,α-二甲基肼甲苯 在 溶剂黄146 、 sodium nitrite 作用下， 以 1,4-二氧六环 为溶剂， 生成 alpha,alpha-二甲基-3,5-二甲氧基苄基-苯丙氨酸
  参考文献：
  名称：

  Derα.α-二甲基-3.5-二甲氧基苄氧基羰基（Ddz）-静态照片和不稳定的Stickstoff-Schutzgruppe for peptidchemie †

  摘要：

  合成α.α-二甲基-3.5-二甲氧基苄氧基羰基叠氮化物（7）和塞纳河畔阿姆塞宗理工学院（Euset vonAminosäurenzu denDdz-aminosäurenwird beschrieben。Es wird gezeigt，daßder neue N -Acyl-Rest leicht unter schwach sauren Bedingungen abgespalten werden kann。奥地利艺术大师，德国艺术大师Schutzgruppe先生，德国UV-Licht ohne Nebenreaktionen zu entfernen博士。国防军和国防军的身份识别和识别。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。

  DOI：

  10.1002/jlac.19727630118

文献信息

• Efficient parallel synthesis of macrocyclic peptidomimetics
  作者：Eric Marsault、Hamid R. Hoveyda、René Gagnon、Mark L. Peterson、Martin Vézina、Carl Saint-Louis、Annick Landry、Jean-François Pinault、Luc Ouellet、Sophie Beauchemin、Sylvie Beaubien、Axel Mathieu、Kamel Benakli、Zhigang Wang、Martin Brassard、David Lonergan、François Bilodeau、Mahesh Ramaseshan、Nadia Fortin、Ruoxi Lan、Shigui Li、Fabrice Galaud、Véronique Plourde、Manon Champagne、Annie Doucet、Patrick Bhérer、Maude Gauthier、Gilles Olsen、Gérald Villeneuve、Shridhar Bhat、Laurence Foucher、Daniel Fortin、Xiaowen Peng、Sylvain Bernard、Alexandre Drouin、Robert Déziel、Gilles Berthiaume、Yves L. Dory、Graeme L. Fraser、Pierre Deslongchamps

  DOI：10.1016/j.bmcl.2008.06.085

  日期：2008.8

  A new method for solid phase parallel synthesis of chemically and conformationally diverse macrocyclic peptidomimetics is reported. A key feature of the method is access to broad chemical and conformational diversity. Synthesis and mechanistic studies on the macrocyclization step are reported.

  报道了一种化学和构象多样的大环拟肽的固相平行合成的新方法。该方法的关键特征是获得广泛的化学和构象多样性。报道了有关大环化步骤的合成和机理研究。
• Methods for preparing anti-hypertensive agents
  申请人：UNIVERSITY OF MIAMI

  公开号：EP0038117A1

  公开（公告）日：1981-10-21

  A plurality of methods are disclosed for preparing compounds having the formula: wherein R is hydrogen, formyl, acetyl, propanoyl, butanoyl, phenylacetyl, phenylpropanoyl, benzoyl, cyclopentanecarbonyl, tert-butyloxycarbonyl, cyclopentanecarbonyl-L-lysyl, pyro-L-glutamyl-L-lysyl, L-lysyl, L-arginyl or pyro-L-glutamyl; A is phenylalanyl, alanyl, tryptophyl, tyrosyl, glycyl isoleucyl, leucyl, histidyl, or valyl, the α-amino group thereof being in amide linkage with R; R1 is hydrogen or methyl, R2 is L-proline, L-3,4-dehydroproline, D,L-3,4-dehydro- proline, L-3-hydroxyproline, L-4-hydroxyproline, L-thiazo- lidine-4-carboxylic acid, or L-5-oxo-proline, the imino group thereof being in imide linkacge with the adiacent and, I n is 0 or 1, such that when n is O, R is methyl, and where n=1, and R1 is methyl the moiety is in the D-configuration. These compounds are inhibitors of angiotensin converting enzyme.

  本发明公开了制备具有以下式子的化合物的多种方法： 其中 R是氢、甲酰基、乙酰基、丙酰基、丁酰基、苯乙酰基、苯丙酰基、苯甲酰基、环戊羰基、叔丁氧羰基、环戊羰基-L-赖氨酰、吡咯-L-谷氨酰-L-赖氨酰、L-赖氨酰、L-精氨酰或吡咯-L-谷氨酰； A 是苯丙氨酰、丙氨酰、色氨酰、酪氨酰、甘氨酰异亮氨酰、亮氨酰、组氨酰或缬氨酰，其 α-氨基与 R 呈酰胺连接； R1 是氢或甲基 R2 是 L-脯氨酸、L-3,4-脱氢脯氨酸、D,L-3,4-脱氢脯氨酸、L-3-羟基脯氨酸、L-4-羟基脯氨酸、L-噻唑-脯氨酸-4-羧酸或 L-5-氧代脯氨酸，其中的亚氨基与邻位的亚氨基连接 和 I n 为 0 或 1，当 n 为 O 时，R 为甲基；当 n=1 时，R1 为甲基。 分子为 D-构型。这些化合物是血管紧张素转换酶的抑制剂。
• Preparation of Photoactivable Amino Acid Derivatives
  作者：Jean-Luc Débieux、Christian G. Bochet

  DOI：10.1021/jo900442p

  日期：2009.6.19

  A range of N-protected-alpha-amino acyl-5,7-dinitroindolines 3a-z were prepared in good yields from commercially available N-protected-alpha-amino acids 1a-z by a two-step sequence of acylation and intramolecular amide N-arylation. Subsequent photochemical acylation of the N-protected-alpha-amino acyl-5,7-dinitroindolines 3e,g,r afforded the corresponding N-protected-alpha-amino acid amides 22e,g,r (77-92%) under mild conditions. All these reactions occurred with complete retention of chirality as evidenced by NMR analysis. This scheme provides an attractive and alternative method to the conventional acylation of alpha-amino acids, especially in cases where the amide bond needs to be formed without the use of a coupling reagent.
• Jensen, Knud J.; Alsina, Jordi; Songster, Michael F., Journal of the American Chemical Society, 1998, vol. 120, # 22, p. 5441 - 5452
  作者：Jensen, Knud J.、Alsina, Jordi、Songster, Michael F.、Vágner, Josef、Albericio, Fernando、Barany, George

  DOI：——

  日期：——
• Optimization of the Potency and Pharmacokinetic Properties of a Macrocyclic Ghrelin Receptor Agonist (Part I): Development of Ulimorelin (TZP-101) from Hit to Clinic
  作者：Hamid R. Hoveyda、Eric Marsault、René Gagnon、Axel P. Mathieu、Martin Vézina、Annick Landry、Zhigang Wang、Kamel Benakli、Sylvie Beaubien、Carl Saint-Louis、Martin Brassard、Jean-François Pinault、Luc Ouellet、Shridhar Bhat、Mahesh Ramaseshan、Xiaowen Peng、Laurence Foucher、Sophie Beauchemin、Patrick Bhérer、Daniel F. Veber、Mark L. Peterson、Graeme L. Fraser

  DOI：10.1021/jm2007062

  日期：2011.12.22

  High-throughput screening of Tranzyme Pharma's proprietary macrocycle library using the aequorin Ca2+-bioluminescence assay against the human ghrelin receptor (GRLN) led to the discovery of novel ago fists against this G-protein coupled receptor. Early hits such as 1 (K-i = 86 nM, EC50 = 134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization. While such macrocycles are not fully rule-of-five compliant, principally due to their molecular weight and clogP, optimization of their pharmacokinetic properties proved feasible largely through conformational rigidification. Extensive SAR led to the identification of 2 (K-i = 16 nM, EC50 = 29 nM), also known as ulimorelin or TZP-101, which has progressed to phase III human clinical trials for the treatment of postoperative ileus. X-ray structure and detailed NMR studies indicated a rigid peptidomimetic portion in 2 that is best defined as a nonideal type-I' beta-turn. Compound 2 is 24% orally bioavailable in both rats and monkeys. Despite its potency, in vitro and in gastric emptying studies, 2 did not induce growth hormone (GH) release in rats, thus demarcating the GH versus GI pharmacology of GRLN.