3-benzamido-3-phenylpropanoic acid methyl ester | 101878-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-benzamido-3-phenylpropanoic acid methyl ester
• 英文别名: N-benzoyl-β-phenylalanine methyl ester；methyl 3-(benzamido)-3-phenylpropanoate；Methyl 3-benzamido-3-phenylpropionate；methyl 3-benzamido-3-phenylpropanoate
• CAS: 101878-00-6
• 化学式: C₁₇H₁₇NO₃
• 分子量: 283.327
• InChiKey: MZWHJSCEBUEVLY-UHFFFAOYSA-N

物化性质

• 沸点：
  490.7±38.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzamido-3-phenylpropanoic acid methyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 丙酮 、 水 为溶剂， 反应 2.0h， 生成 3-苯甲酰氨基-3-苯基丙酸
  参考文献：
  名称：

  Synthesis, in Vitro and in Vivo Biological Evaluation, Docking Studies, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronic Acid Proteasome Inhibitors Composed of β-Amino Acids

  摘要：

  A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i wits the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active its the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 mu M against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in it similar way as bortezomib.

  DOI：

  10.1021/jm901407s
• 作为产物：
  描述：

  DL-3-氨基-3-苯基丙酸 在 sodium hydroxide 、 氯化亚砜 作用下， 反应 12.5h， 生成 3-benzamido-3-phenylpropanoic acid methyl ester
  参考文献：
  名称：

  恶嗪酮的动力学拆分：对映体纯的β-氨基酸的有机催化方法。

  摘要：

  DOI：

  10.1002/anie.200502003

文献信息

• Catalytic, One-Pot Synthesis of β-Amino Acids from α-Amino Acids. Preparation of α,β-Peptide Derivatives
  作者：Carlos Saavedra、Rosendo Hernández、Alicia Boto、Eleuterio Álvarez

  DOI：10.1021/jo9004487

  日期：2009.7.3

  The one-pot conversion of readily available α-amino acid into β-amino acid derivatives was carried out in good yields. The method is a sequential process initiated by a tandem radical decarboxylation−oxidation reaction; the resulting acyliminium ion was trapped by silyl ketenes. Stoichiometric and catalytic versions of this reaction were developed and then applied to prepare modified di- and tripeptides

  容易获得的α-氨基酸一锅转化为β-氨基酸衍生物的收率很高。该方法是由串联自由基脱羧氧化反应引发的顺序过程。所得的丙烯酰亚胺离子被甲硅烷基烯酮捕获。开发了该反应的化学计量和催化形式，然后用于制备修饰的二肽和三肽。有趣的是，一些三肽在固态下形成了扩展的β-转角。
• Synthesis and Ring Opening of Methyl 2-Alkyl-3-(alkyl/aryl)-1-benzoylaziridine-2-carboxylates: Synthesis of Polysubstituted Amino Acids
  作者：Carmela Papa、Claudia Tomasini

  DOI：10.1002/(sici)1099-0690(200004)2000:8<1569::aid-ejoc1569>3.0.co;2-x

  日期：2000.4

  A new method for the preparation of 2,2,3-trisubstituted methyl 1-benzoylaziridine-2-carboxylates is reported. These compounds have been obtained starting from α-alkyl β-amino acids by formation of the lithium dianion and reaction with iodine. The aziridines undergo ring expansion or ring opening, depending on the substituents of the aziridine ring and on the reaction conditions. Following these methods

  报道了一种制备 2,2,3-三取代甲基 1-benzoylaziridine-2-carboxylates 的新方法。这些化合物是从α-烷基β-氨基酸开始，通过形成锂二价阴离子并与碘反应获得的。氮丙啶会发生扩环或开环，这取决于氮丙啶环的取代基和反应条件。按照这些方法，已经合成了α-取代的α-羟基β-氨基酸和α-取代的β-羟基α-氨基酸。
• Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids
  作者：Yongqiang Zhu、Gang Wu、Xinrong Zhu、Yuheng Ma、Xin Zhao、Yuejie Li、Yunxia Yuan、Jie Yang、Sen Yu、Feng Shao、Meng Lei

  DOI：10.1021/jm1009742

  日期：2010.12.23

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.
• Enzymatic resolution of N-protected-β3-amino methyl esters, using lipase B from Candida antarctica
  作者：Patricia Flores-Sánchez、Jaime Escalante、Edmundo Castillo

  DOI：10.1016/j.tetasy.2004.11.082

  日期：2005.2

  Racemic beta(3)-amino methyl esters bearing the amine function protected with Bz, Cbz, Boc, Fmoc and as aminobenzamide, were resolved by enantiospecific transesterifications catalyzed by lipase B from Candida antarctica. The reactions proceeded with a high conversion and yielded enantiomerically pure enantiomers. (C) 2004 Elsevier Ltd. All rights reserved.
• A facile and stereocontrolled synthesis of syn-α-alkyl α-hydroxy β-amino acids
  作者：Alessandra Maria Nocioni、Carmela Papa、Claudia Tomasini

  DOI：10.1016/s0040-4039(99)01772-4

  日期：1999.11

  The diastereoselective synthesis of syn-alpha-alkyl alpha-hydroxy beta-amino acids 4a-h was easily accomplished by reaction of the sodium dianion of the corresponding anti alpha-alkyl beta-benzoylamino acid methyl eaters with iodine. The intermediate alpha-iodo derivatives spontaneously afforded cis-oxazolines which, upon hydrolysis, provided the desired products, with diastereoselectivities up to 99:1. (C) 1999 Elsevier Science Ltd. All rights reserved.