(S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-methylbutanoate | 53159-55-0

• 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: (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-methylbutanoate
• 英文别名: Cbz-Ala-Val-O^tBu；(+)-tert-butyl-(N'-benzyloxycarbonyl-L-alanyl)-L-valinate；Benzyloxycarbonyl-L-alanyl-L-valine tert-butyl ester；tert-butyl (2S)-3-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]butanoate
• CAS: 53159-55-0
• 化学式: C₂₀H₃₀N₂O₅
• 分子量: 378.469
• InChiKey: KTZPRANHFVVSIF-HOCLYGCPSA-N

物化性质

• 沸点：
  531.2±40.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-methylbutanoate 在 palladium on activated charcoal 、 氢气 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -15.0~25.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 Cbz-Thr-Ser-Ala-Val
  参考文献：
  名称：

  Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases

  摘要：

  Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.

  DOI：

  10.1016/j.ejmech.2012.10.053
• 作为产物：
  描述：

  Z-Val-O-t-Bu 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-methylbutanoate
  参考文献：
  名称：

  多肽。第二十四部分。壬酸的合成

  摘要：

  已经合成了L-和D -3-羟基十二烷酰基甘氨酰-L-戊酰基-D-亮基-L-丙氨酰基-D-缬氨酸（IV）及其甲酯。衍生自D-羟基酸的化合物与异丁酸和异丁酸甲酯没有区别。这证实isariin的氨基酸序列，的代谢物棒束孢cretacea中释放于碱性水解isariic酸。可以预见的是，环化六肽（IV）的尝试没有成功。这可以归因于C末端缬氨酸残基的存在。

  DOI：

  10.1039/p19740000796

文献信息

• METHOD FOR PRODUCING AMIDE COMPOUND
  申请人：CHUBU UNIVERSITY EDUCATIONAL FOUNDATION

  公开号：US20200131117A1

  公开（公告）日：2020-04-30

  Provided is a novel method for producing amide compounds at high stereochemical selectivities. The method according to the present invention for producing amide compounds is provided with an amidation step for reacting, in the presence of a catalyst comprising a metal compound, an amino compound with an aminoester compound represented by general formula (1) to amidate the ester group in the aminoester compound.

  提供了一种新颖的方法，用于以高立体化学选择性制备酰胺化合物。根据本发明的制备酰胺化合物的方法包括在存在包含金属化合物的催化剂的情况下，进行酰胺化步骤，将氨基化合物与通式（1）所代表的氨基酯化合物反应，以使氨基酯化合物中的酯基酰胺化。
• Stereocontrolled [¹¹ C]Alkylation of N-Terminal Glycine Schiff Bases To Obtain Dipeptides
  作者：Ulrike Filp、Aleksandra Pekošak、Alex J. Poot、Albert D. Windhorst

  DOI：10.1002/ejoc.201701129

  日期：2017.10.10

  stereoselective radiochemical [11C]alkylation to obtain functionalized dipeptides. We herein report a broadly applicable procedure for the asymmetric [11C]alkylation of dipeptides to give labeled N-terminal peptides by using different [11C]alkyl halides. Contended stereoselectivities of the reactions were observed by using 11C-labeled alkyl halides, [11C]methyl iodide and [11C]benzyl iodide, and diastereomeric

  使用各种季铵盐作为手性相转移催化剂可以进行有效的立体选择性放射化学 [11C] 烷基化，以获得功能化的二肽。我们在此报告了一种广泛适用的程序，用于二肽的不对称 [11C] 烷基化，通过使用不同的 [11C] 烷基卤化物得到标记的 N 端肽。通过使用 11C 标记的烷基卤化物、[11C] 甲基碘和 [11C] 苄基碘，观察到反应的立体选择性，并分别实现了 95:5 和 90:10 的不同专用催化剂的非对映体比例。因此，对映体富集化合物的直接合成应该在基于肽的放射性药物开发和正电子发射断层扫描成像中发挥重要作用。
• Amide Formation in One Pot from Carboxylic Acids and Amines via Carboxyl and Sulfinyl Mixed Anhydrides
  作者：Bartosz K. Zambroń、Srinivas R. Dubbaka、Dean Marković、Elena Moreno-Clavijo、Pierre Vogel

  DOI：10.1021/ol401053y

  日期：2013.5.17

  An efficient method has been developed for the preparation of yet unknown acyclic mixed anhydrides of carboxylic and sulfinic acids. Sterically hindered 2-methylbut-3-ene-2-sulfinyl carboxylates add primary and secondary amines preferentially onto the carbonyl moieties realizing a new method for the one-pot preparation of carboxamides. It uses 1:1 mixtures of carboxylic acids and amines without a base

  已经开发了一种有效的方法来制备未知的羧酸和亚磺酸的无环混合酸酐。受位阻的2-甲基丁-3-烯-2-亚磺酰基羧酸酯优先将伯胺和仲胺添加到羰基部分上，实现了一种一锅法制备羧酰胺的新方法。它使用不带碱的1：1羧酸和胺混合物，不需要过量的试剂，仅释放挥发性副产物。通过应用该方法，可以在溶液中制备受保护的二肽和三肽，而没有差向异构化。
• Total Synthesis and Determination of the Absolute Configuration of Guadinomines B and C₂
  作者：Tomoyasu Hirose、Toshiaki Sunazuka、Satoshi Tsuchiya、Toshiaki Tanaka、Yasuhiro Kojima、Ryuma Mori、Masato Iwatsuki、Satoshi Ōmura

  DOI：10.1002/chem.200801024

  日期：2008.9.19

  describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could

  本文介绍了胍基亚胺的绝对构型的测定，其是细菌的III型分泌系统（TTSS）抑制剂的新型环状胍基天然产物。任何会中断细菌TTSS的化合物都可能是理想的抗感染药。可靠的不对称合成胍基亚胺揭示了它们的绝对构型，如果没有这种合成方法就无法确定。我们的报告不仅描述了标题化合物的不对称全合成，而且还证明了三取代的哌嗪酮核的新颖简明合成方法为光学纯形式。我们的方法的新功能是分子内S（N）2环化，使用PPh（3）和I（2）构造独特的5元环胍亚结构。
• Polypeptides and methods of preparation
  申请人：——

  公开号：US04237046A1

  公开（公告）日：1980-12-02

  There are disclosed active fragments of vasoactive peptides and methods of preparation. The active fragments comprise the following amino acid sequences: (a) X-MET-ALA-VAL-X.sub.1 (b) X-MET-ALA-VAL-LYS-X.sub.1 (c) X-MET-ALA-VAL-LYS-LYS-TYR-LEU-ASN-SER-Y-LEU-Z-X.sub.1 wherein X is hydrogen, glutamyl, or pyroglutamyl, X.sub.1 is OH or NH.sub.2 ; Y is ILE or VAL; and Z is ASN or THR.

  公开了血管活性肽的活性片段和制备方法。这些活性片段包括以下氨基酸序列：(a) X-MET-ALA-VAL-X.sub.1 (b) X-MET-ALA-VAL-LYS-X.sub.1 (c) X-MET-ALA-VAL-LYS-LYS-TYR-LEU-ASN-SER-Y-LEU-Z-X.sub.1，其中X为氢、谷氨酰或吡啶酰，X.sub.1为OH或NH.sub.2；Y为ILE或VAL；Z为ASN或THR。