2R,3S-2-[(tert-butoxy)carbonylamino]-3-phenylmethoxybutanoic acid

• 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: 2R,3S-2-[(tert-butoxy)carbonylamino]-3-phenylmethoxybutanoic acid
• 英文别名: Boc-Thr(Bzl)-NH2；tert-butyl ((2S,3R)-1-amino-3-(benzyloxy)-1-oxobutan-2-yl)carbamate；Boc-Thr(Bzl)-OH；tert-butyl N-[(2S,3R)-1-amino-1-oxo-3-phenylmethoxybutan-2-yl]carbamate
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: OCFYTKZXDSNICX-YPMHNXCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2R,3S-2-[(tert-butoxy)carbonylamino]-3-phenylmethoxybutanoic acid 在 甲酸 作用下， 反应 18.0h， 生成 Thr(Bzl)-NH2
  参考文献：
  名称：

  组织蛋白酶 B 和 L 腈基抑制剂的设计、合成和逐步优化

  摘要：

  人组织蛋白酶 B (CatB) 是癌症治疗中的重要生物学靶点。在这项工作中，我们采用了一种基于知识的设计方法，并合成了一组新的 19 种肽样腈基组织蛋白酶抑制剂。针对一组人半胱氨酸蛋白酶对报告的化合物进行了分析：CatB、CatL、CatK 和 CatS。三种化合物（7h、7i和7j）显示出对 CatB 的纳摩尔抑制以及对 CatK 和 CatL 的选择性。的选择性通过使用的组合来实现对位联苯环在P 3，卤代苯丙氨酸P 2和Thr-O-BZ组在P 1。同样地，化合物7I和7J在所研究的酶组中显示出选择性 CatB 抑制作用。我们还描述了一个成功的例子，用生物等排置换磺酰胺 [ 7e  →  6b ]的酰胺键，我们观察到 CatB 的亲和力和选择性增加，同时降低了化合物的亲脂性 (ilogP)。我们基于知识的设计方法和各自的结构-活性关系为治疗相关组织蛋白酶的特定配体-靶标相互作用提供了见解。

  DOI：

  10.1016/j.bmc.2020.115827
• 作为产物：
  描述：

  N-Boc-O-苄基-L-苏氨酸 在 N,N-二异丙基乙胺 、 氯甲酸异丁酯 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 20.5h， 以65%的产率得到2R,3S-2-[(tert-butoxy)carbonylamino]-3-phenylmethoxybutanoic acid
  参考文献：
  名称：

  用新的二肽基腈抑制剂作为锥虫杀虫剂定位半胱氨酸蛋白酶的S1和S1'亚位点。

  摘要：

  半胱氨酸蛋白酶Cruzipain被认为是治疗南美锥虫病的有效治疗靶标。设计，合成了一系列26种新化合物，并针对重组Cruzain（Cz）进行了测试，以绘制其S1 / S1´子位图。在一组四个人类半胱氨酸蛋白酶（CatB，CatK，CatL，CatS）和墨西哥利什曼原虫CPB（一组可能是治疗皮肤利什曼病的潜在靶标）上对同一系列进行了评估。合成的化合物是基于P1（十个），P2（六个）和P3（四个不同的结构单元）中不同部分最有希望的组合而设计的二肽基腈。八个化合物的Cz的Ki小于20.0 nM，而三个化合物的LmCPB符合这些标准。三种抑制剂的EC50值为ca。4.0微米 因此，根据其抗胰锥作用，与苯硝唑相当。我们的作图方法和各自的结构活性关系为治疗相关的半胱氨酸蛋白酶的特定配体-靶标相互作用提供了见识。

  DOI：

  10.1371/journal.pntd.0007755

文献信息

• Convenient Synthesis of<i>N</i>-Protected Amino Acid Amides
  作者：Sukekatsu Nozaki、Ichiro Muramatsu

  DOI：10.1246/bcsj.61.2647

  日期：1988.7

  Boc- or Z-amino acids were conveniently amidated at room temperature by a one-pot procedure employing ammonium hydrogencarbonate and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in yields of 81–96%. The benzyl ester-type protector for the side chains of aspartic acid and glutamic acid was not affected by the procedure.

  Boc-或Z-氨基酸通过采用碳酸氢铵和N-乙氧羰基-2-乙氧基-1,2-二氢喹啉的一锅法工艺，在室温下方便地进行酰胺化，产率为81-96%。该工艺不会影响天冬氨酸和谷氨酸侧链的苄酯型保护基。
• A selective method for the preparation of primary amides: Synthesis of Fmoc-l-4-carboxamidophenylalanine and other compounds
  作者：Wei Wang、John S. McMurray

  DOI：10.1016/s0040-4039(99)00245-2

  日期：1999.3

  A new method for the synthesis of primary amides was developed in which carboxylic acids were treated with ammonium chloride in the presence of peptide synthesis coupling agents and base at room temperature. These mild conditions allow the conversion of carboxyl groups to primary amides on substrates possessing sensitive functional groups such as esters and the base-labile Fmoc protecting group.

  开发了一种新的合成伯酰胺的方法，其中在肽合成偶联剂和碱存在下，在室温下用氯化铵处理羧酸。这些温和的条件使羧基能够在具有敏感官能团（例如酯和对碱不稳定的Fmoc保护基）的底物上转化为伯酰胺。
• Development of a Method for the Preparation of α-Azido-Masked Acyl Cyanides, Synthetic Equivalents of N-Protected–C-Activated α-Amino Acids
  作者：Hisao Nemoto、Rujian Ma、Touru Ibaragi、Ichiro Suzuki、Masayuki Shibuya

  DOI：10.1016/s0040-4020(00)00040-5

  日期：2000.3

  preparation of α-azido-masked acyl cyanides as synthetic equivalents of N-protected–C-activated α-amino acids was developed using carbon–carbon bond formation between aldehydes and the Masked Acyl Cyanide Reagents, followed by sulfonylation and substitution by azide anion. This method was applied to the synthesis of d-threonine and l-allo-threonine derivatives.

  一种用于α叠氮基掩蔽酰基氰化物作为合成等同物的制备方法Ñ -protected- Ç活化α氨基酸用醛和碳之间-碳键形成开发掩敝酰基试剂的氰化物，随后磺酰和取代叠氮化物阴离子。这种方法适用于d苏氨酸和1-合成异体苏氨酸衍生物。
• Optimization strategy of single-digit nanomolar cross-class inhibitors of mammalian and protozoa cysteine proteases
  作者：Lorenzo Cianni、Fernanda dos Reis Rocho、Fabiana Rosini、Vinícius Bonatto、Jean F.R. Ribeiro、Jerônimo Lameira、Andrei Leitão、Anwar Shamim、Carlos A. Montanari

  DOI：10.1016/j.bioorg.2020.104039

  日期：2020.8

  Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-based probes for diagnostic and mechanistic purposes that are critical in health and disease. In this paper, we present the modulation of a CP panel of parasites and mammals (Trypanosoma cruzi cruzain, LmCPB, CatK, CatL and CatS), whose inhibition by nitrile peptidomimetics allowed the identification of specificity and selectivity for a given CP. The activity cliffs identified at the CP inhibition level are useful for retrieving trends through multiple structure-activity relationships. For two of the cruzain inhibitors (10g and 4e), both enthalpy and entropy are favourable to Gibbs binding energy, thus overcoming enthalpy-entropy compensation (EEC). Group contribution of individual molecular modification through changes in enthalpy and entropy results in a separate partition on the relative differences of Gibbs binding energy (Delta Delta G). Overall, this study highlights the role of CPs in polypharmacology and multi-target screening, which represents an imperative trend in the actual drug discovery effort.
• Structure–activity relationships of bacterial outer-membrane permeabilizers based on polymyxin B heptapeptides
  作者：Hirotoshi Urakawa、Keiichi Yamada、Keiko Komagoe、Setsuko Ando、Hiroyuki Oku、Takashi Katsu、Ichiro Matsuo

  DOI：10.1016/j.bmcl.2010.01.040

  日期：2010.3

  A series of cationic cyclic heptapeptides based on polymyxin B have been synthesized for use as permeabilizers of the outer membrane of Gram-negative bacteria. Only analogs with the Dab(2)-D-Phe(3)-Leu(4)-Xxx(5) sequence (Xxx = Dab or Orn) showed a synergistic bactericidal effect when combined with conventional antibiotics, indicating that the Dab(2) residue plays a critical role in permeation of the outer membrane of Gram-negative bacteria. (C) 2010 Elsevier Ltd. All rights reserved.