N-Cbs-L-Ala-OPiv | 209113-00-8

• 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: N-Cbs-L-Ala-OPiv
• 英文别名: (S)-2-Benzyloxycarbonylaminopropionic acid-2,2-dimethyl-propionic acid anhydride；[(2S)-2-(phenylmethoxycarbonylamino)propanoyl] 2,2-dimethylpropanoate
• CAS: 209113-00-8
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: HXLFRRYVZGKYDW-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Cbs-L-Ala-OPiv 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 17.17h， 生成
  参考文献：
  名称：

  Potent Proteasome Inhibitors Derived from the Unnatural cis-Cyclopropane Isomer of Belactosin A: Synthesis, Biological Activity, and Mode of Action

  摘要：

  The natural product belactosin A (1) with a trans-cyclopropane structure is a useful prototype compound for developing potent proteasome (core particle, CP) inhibitors. To date, 1 and its analogues are the only CP ligands that bind to both the nonprimed S1 pocket as well as the primed substrate binding channel; however, these molecules harbor a high IC50 value of more than 1 mu M. We have performed structure activity relationship studies, thereby elucidating unnatural cis-cyclopropane derivatives of 1 that exhibit high potency to primarily block the chymotrypsin-like active site of the human constitutive (cCP) and immunoproteasome (iCP). The most active compound 3e reversibly inhibits cCP and iCP similarly with an IC50 of 5.7 nM. X-ray crystallographic analysis of the yeast proteasome in complex with 3e revealed that the ligand is accommodated predominantly into the primed substrate binding channel and covalently binds to the active site threonine residue via its beta-lactone ring-opening.

  DOI：

  10.1021/jm4002296
• 作为产物：
  描述：

  苄氧羰基-L-丙氨酸 、 三甲基乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 N-Cbs-L-Ala-OPiv
  参考文献：
  名称：

  Belactosin A及其立体和区域异构体的三维结构-活性关系研究：通过立体化学多样性导向的策略开发有效的蛋白酶体抑制剂†

  摘要：

  研究了基于构象刚性环丙烷结构的基于立体化学多样性导向策略的有效蛋白酶体抑制剂的开发。因此，设计了一系列的Belactosin A（2）立体异构体和区域异构体，这是一种含有环丙烷氨基酸（甲氨基氨基酸）的三肽蛋白酶体抑制剂，其中中央的环丙烷氨基酸部分被相应的立体异构体或区域异构体。使用一系列立体异构体的环丙烷氨基酸等效物，具有顺/反，D / L和syn / anti我们先前开发的立体化学多样性作为关键单元，已成功合成了目标化合物。生物学评价表明，如所预期，化合物活性改取决于中心环丙烷氨基酸部分的立体化学：在反式/ L-顺式异构体7和所述顺式/ L-抗-异构体9分别超过两倍强效天然Belactosin A（反式/ L-反异构体）。此外，三肽化合物13，非天然的顺式/ L-抗异构体9的合成前体被鉴定为高效蛋白酶体抑制剂。该化合物的效力是贝洛斯托因A的20倍，甚至比众所周知的抑制剂乳腺抑肽（4）更有

  DOI：

  10.1039/b900384c

文献信息

• Synthesis of fragments of anglerfish pre-proglucagon i mid ii (AGFI and AGFII)
  作者：I.J. Galpin、C.A. Leach

  DOI：10.1016/s0040-4020(01)98817-9

  日期：——

  Four fragments of the two pre-proglucagons from the Anglerfish (Lophius americanus) have been synthesised. The fragments, AGFI (35-40) and (105-110), and AGFII (34-38) and (103-108) were prepared by solution peptide synthesis using a combination of hydrogenolysable and acid labile protecting groups. The pivalic mixed anhydride method was generally used for coupling although occasionally the DCCI/HOBt

  合成了来自Anglerfish（American Lophius americanus）的两个前胰高血糖素原的四个片段。片段AGFI（35-40）和（105-110）以及AGFII（34-38）和（103-108）通过使用可水解和酸不稳定的保护基团的溶液肽合成制备。尽管有时使用DCCI / HOBt方法，但通常使用特戊性混合酸酐法进行偶联。使用三氟乙酸最终去除了酸不稳定的保护基。
• Process for the preparation of mixed anhydrides
  申请人：——

  公开号：US20020077481A1

  公开（公告）日：2002-06-20

  The present invention is concerned with an improved process for the manufacture of mixed anhydrides. The process comprises adding an adjuvant base to a mixture of acid and reactive acid derivative. It is especially suitable for use in the synthesis of peptides and/or for the manufacture of pharmaceutically active substances or corresponding intermediates.

  本发明涉及一种改进的混合酸酐制造过程。该过程包括向酸和反应性酸衍生物的混合物中添加辅助碱。它特别适用于合成肽和/或制造药用活性物质或相应中间体。
• Investigation of the Noncovalent Binding Mode of Covalent Proteasome Inhibitors around the Transition State by Combined Use of Cyclopropylic Strain-Based Conformational Restriction and Computational Modeling
  作者：Shuhei Kawamura、Yuka Unno、Motohiro Tanaka、Takuma Sasaki、Akihito Yamano、Takatsugu Hirokawa、Tomoshi Kameda、Akira Asai、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1021/jm400542h

  日期：2013.7.25

  To develop potent covalent inhibitors, the noncovalent interactions around the transition state to form covalent bonding should be optimized because the potency of the inhibitor can be depending on the energy of the transition state. Here, we report an efficient analysis of the noncovalent binding mode of a potent covalent proteasome inhibitor 3a around the transition state by a combined use of the

  为了开发有效的共价抑制剂，应当优化过渡态周围形成共价键的非共价相互作用，因为抑制剂的效能可能取决于过渡态的能量。在这里，我们报告了通过结合使用化学方法（即基于环丙基菌株的构象限制和计算对接方法）对有效的共价蛋白酶体抑制剂3a在过渡态附近的非共价结合模式的有效分析。此外，我们利用本研究构建的蛋白酶体模拟模型，计算了过渡态周围预测的非共价复合物中一系列盐基孢酰胺衍生物的结合能，这与它们的pIC 50密切相关。因此，提出的预测共价抑制剂过渡态附近非共价结合模式的对接方法将有助于共价抑制剂的开发。
• Synthesis of 2,3- and 3,4-Methanoamino Acid Equivalents with Stereochemical Diversity and Their Conversion into the Tripeptide Proteasome Inhibitor Belactosin A and Its Highly Potent <i>Cis</i>-Cyclopropane Stereoisomer
  作者：Keisuke Yoshida、Kazuya Yamaguchi、Takayuki Sone、Yuka Unno、Akira Asai、Hideyoshi Yokosawa、Akira Matsuda、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1021/ol8013304

  日期：2008.8.21

  A series of chiral 2,3- and 3,4-methanoamino acid equivalents of stereochernical diversity were designed and synthesized from our chiral cyclopropane units, using a diastereoselective Grignard addition with (R)- or (S)-t-butanesulfinyl imines as the key step. These equivalents were converted into the proteasome inhibitor belactosin A and its cis-cyclopropane stereoisomer. The unnatural cis-isomer was shown to be more than twice as potent as belactosin A as a proteasome inhibitor.
• Verfahren zur Herstellung gemischter Anhydride
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0847994B1

  公开（公告）日：2003-04-09