N-carbobenzyloxy-2,2-diphenylglycine | 95166-02-2

• 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: N-carbobenzyloxy-2,2-diphenylglycine
• 英文别名: N-Cbz-diphenylglycine；2,2-diphenyl-2-(phenylmethoxycarbonylamino)acetic acid
• CAS: 95166-02-2
• 化学式: C₂₂H₁₉NO₄
• 分子量: 361.397
• InChiKey: YGVUXXXYGJJVJU-UHFFFAOYSA-N

物化性质

• 熔点：
  96.5 °C
• 沸点：
  568.2±50.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-carbobenzyloxy-2,2-diphenylglycine 在 N-甲基吗啉 、 氢溴酸 、 1-羟基苯并三唑 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 Z-Val-Dph-Val-OMe
  参考文献：
  名称：

  Dramatic Differences in the Effectiveness among Various Coupling Methods in the Synthesis of Peptides Containing α,α-Diphenylglycine

  摘要：

  通过各种方法将 N-苄氧羰基-α,α-二苯基甘氨酸（Z-Dph）与各种氨基酸的甲酯（AA-OMe）偶联，以及将 Z-AA 与 Dph-OMe 偶联，可分别得到 Z-Dph-AA-OMe 和 Z-AA-Dph-OMe。根据所采用的偶联方法，二肽的产率从 90% 以上到 0% 不等。

  DOI：

  10.1246/cl.1993.1583
• 作为产物：
  描述：

  氯甲酸苄酯 、 2,2-二苯基甘氨酸 在 盐酸 、 锌 作用下， 以 水 、 乙腈 为溶剂， 以69%的产率得到N-carbobenzyloxy-2,2-diphenylglycine
  参考文献：
  名称：

  Babu, Vommina V. Suresh; Ananda, Kuppanna, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 1, p. 70 - 74

  摘要：

  DOI：

文献信息

• Chemical communication: conductors and insulators of screw-sense preference between helical oligo(aminoisobutyric acid) domains
  作者：Thomas Boddaert、Jordi Solà、Madeleine Helliwell、Jonathan Clayden

  DOI：10.1039/c2cc00060a

  日期：——

  1H NMR studies quantify the abilities of achiral amino acids to communicate a left-handed screw-sense preference from one helical Aib4 domain to another: certain quaternary amino acids (e.g. Ac6c) act as effective conductors of conformational preference while others (e.g. diphenylglycine) acts as insulators.

  1H NMR研究表明，非手性氨基酸能够传递从螺旋Aib4结构域到另一个结构域的左旋螺向偏好：某些四级氨基酸（如Ac6c）能有效传递构象偏好，而其他氨基酸（如双苯甘氨酸）则起到绝缘体的作用。
• In-Depth Study of Tripeptide-Based α-Ketoheterocycles as Inhibitors of Thrombin. Effective Utilization of the S₁‘ Subsite and Its Implications to Structure-Based Drug Design
  作者：Michael J. Costanzo、Harold R. Almond、Leonard R. Hecker、Mary R. Schott、Stephen C. Yabut、Han-Cheng Zhang、Patricia Andrade-Gordon、Thomas W. Corcoran、Edward C. Giardino、Jack A. Kauffman、Joan M. Lewis、Lawrence de Garavilla、Barbara J. Haertlein、Bruce E. Maryanoff

  DOI：10.1021/jm0303857

  日期：2005.3.1

  structures of the ternary complexes 3-thrombin-hirugen and 4-thrombin-hirugen depict novel interactions in the S(1)' region, with the benzothiazole ring forming a hydrogen bond with His-57 and an aromatic stacking interaction with Trp-60D of thrombin's insertion loop. The benzothiazole ring of 3 displaces the Lys-60F side chain into a U-shaped gauche conformation, whereas the benzothiazole carboxylate

  凝血酶抑制剂由于其抗凝和抗血栓形成作用而可能在医学上有用。我们基于d-Phe-Pro-Arg以及相关的凝血酶活性位点识别基序合成和评估了各种杂环活化的酮，作为候选抑制剂。基于肽的α-酮杂环通常通过亚氨酸酯或Weinreb酰胺途径制备（方案1和2），事实证明后者更为普遍。通常测定测试化合物对人α-凝血酶和牛胰蛋白酶的抑制作用。从基于结构的设计角度来看，杂环允许人们探索和调节凝血酶S1'亚位点内的相互作用。优选的α-酮杂环是富含pi的2取代的吡咯，在带有酮基的碳原子的附近至少有两个杂原子，优选的凝血酶抑制剂是2-酮基苯并噻唑3，其有效K（i）值为0.2 nM，约为1。选择性比胰蛋白酶高15倍。2-酮苯并噻唑13表现出极强的凝血酶抑制作用（K（i）= 0.000 65 nM;缓慢紧密结合）。几个α-酮杂环化合物的凝血酶K（i）值在0.1-400 nM范围内。在温和的碱性条件下，α-酮杂环的“ A
• Mechanism of the Pd-catalyzed Decarboxylative Allylation of α-Imino Esters: Decarboxylation via Free Carboxylate Ion
  作者：Zhe Li、Yuan-Ye Jiang、Andrew A. Yeagley、James P. Bour、Lei Liu、Jason J. Chruma、Yao Fu

  DOI：10.1002/chem.201201425

  日期：2012.11.5

  The Pd‐catalyzed decarboxylative allylation of α‐(diphenylmethylene)imino esters (1) or allyl diphenylglycinate imines (2) is an efficient method to construct new C(sp3)C(sp3) bonds. The detailed mechanism of this reaction was studied by theoretical calculations [ONIOM(B3LYP/LANL2DZ+p:PM6)] combined with experimental observations. The overall catalytic cycle was found to consist of three steps: oxidative

  Pd催化的α-（二苯基亚甲基）亚氨基酯（1）或烯丙基二苯基甘氨酸亚胺（2）的脱羧烯丙基化是构建新的C（sp 3）C（sp 3）键的有效方法。通过理论计算[ONIOM（B3LYP / LANL2DZ + p：PM6）]结合实验观察，研究了该反应的详细机理。发现整个催化循环包括三个步骤：氧化加成，脱羧和还原烯丙基化。1对[（dba）Pd（PPh 3）2的氧化加成]（dba ＝二亚苄基丙酮）产生烯丙基钯阳离子和具有+ 9.1kcal mol -1的低活化势垒的羧酸根阴离子。以下确定速率的脱羧反应是通过溶剂暴露的α-亚氨基羧酸羧酸根阴离子，而不是活化障碍为+22.7 kcal mol -1的O-连接的烯丙基钯羧酸盐进行的。由这种脱羧作用生成的2-氮杂烯丙基阴离子在外球过程中攻击与Pd中心相对的烯丙基配体的表面，从而产生主要产物3，其活化势垒低于次要产物4。与观测到的区域选择性呈正线性Hammett相关性[
• Grzegorzewska,U. et al., Bulletin de l'Academie Polonaise des Sciences, Serie des Sciences Chimiques, 1974, vol. 22, p. 679 - 683
  作者：Grzegorzewska,U. et al.

  DOI：——

  日期：——
• Synthesis and anticonvulsant activity of 2-iminohydantoins
  作者：Chul Hoon Kwon、Muhammad Tahir Iqbal、John N. D. Wurpel

  DOI：10.1021/jm00110a013

  日期：1991.6

  Iminohydantoins selectively substituted at position C-5 and their 1-carbobenzoxy derivatives have been synthesized, and their anticonvulsant activity was evaluated in mice. In general the more lipophilic 1-carbobenzoxy iminohydantoins were more potent than the unsubstituted counterparts. Evaluation of the individual enantiomers of the chiral iminohydantoins showed that the anticonvulsant activity resided primarily in the S isomers. In this study, (S)-(+)-1-carbobenzoxy-5-isobutyl-2-iminohydantoin (9a) was the most active member. This compound was not nearly as active as phenytoin against electrically induced convulsions, but was also active against pentylenetetrazole-induced seizures, suggesting a broader clinical potential. The closest analogue of phenytoin, viz., 5,5-diphenyl-2-iminohydantoin (1), failed to show any significant activity. Methylation on N-3 or the imino nitrogen of 1 also did not provide a compound with substantial activity. 2-Thiophenytoin was not active against electroshock seizures and showed only a weak activity against pentylenetetrazole. This study suggested that the structure-activity relationship of 2-iminohydantoins was quite different from that of 2-hydantoins.