methyl (2S)-2-{[(benzyloxy)carbonyl](tert-butoxycarbonyl)amino}-5-oxopentanoate | 952661-09-5

• 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: methyl (2S)-2-{[(benzyloxy)carbonyl](tert-butoxycarbonyl)amino}-5-oxopentanoate
• 英文别名: methyl (2S)-2-[(benzoxycarbonyl)(tert-butoxycarbonyl)amino]-5-oxopentanoate；methyl (S)-2-(((benzyloxy)carbonyl)(tert-butoxycarbonyl)amino)-5-oxopentanoate；methyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]-5-oxopentanoate
• CAS: 952661-09-5
• 化学式: C₁₉H₂₅NO₇
• 分子量: 379.41
• InChiKey: UIWDHUBCCQWKIY-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  99.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-{[(benzyloxy)carbonyl](tert-butoxycarbonyl)amino}-5-oxopentanoate 在 溶剂黄146 、 三氟乙酸 、 silver(l) oxide 作用下， 以 氯仿 为溶剂， 反应 8.5h， 生成 1-benzyl 2-methyl (2S)-5-((1-adamantyloxy){2-[(2-oxo-2-phenylethoxy)carbonyl]-4-pentynyl}phosphoryl)tetrahydro-1H-pyrrole-1,2-dicarboxylate
  参考文献：
  名称：

  A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics

  摘要：

  [GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.

  DOI：

  10.1021/jo071081l
• 作为产物：
  描述：

  dimethyl (S)-N-(benzyloxycarbonyl)glutamate 在 4-二甲氨基吡啶 、 二异丁基氢化铝 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 4.17h， 生成 methyl (2S)-2-{[(benzyloxy)carbonyl](tert-butoxycarbonyl)amino}-5-oxopentanoate
  参考文献：
  名称：

  A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics

  摘要：

  [GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.

  DOI：

  10.1021/jo071081l

文献信息

• Protein synthesis with conformationally constrained cyclic dipeptides
  作者：Chao Zhang、Xiaoguang Bai、Larisa M. Dedkova、Sidney M. Hecht

  DOI：10.1016/j.bmc.2020.115780

  日期：2020.11

  two 7-membered cyclic acylhydrazides (4 and 5) by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI)-mediated cyclization of amino acids having selectively protected hydrazine functional groups in their side chains. In common with the lactam dipeptides, acylhydrazide dipeptides 4 and 5 could be used to activate the same suppressor tRNA transcript and to incorporate the cyclic dipeptides into DHFR. They

  我们已经合成了几种构象受限的二肽类似物作为掺入蛋白质的可能底物。这些包括由 2,4-二氨基丁酸、鸟氨酸和赖氨酸的 Boc 衍生物形成的三种环状二肽，分别具有 5、6 和 7 元内酰胺环。这些二肽用于激活抑制性 tRNA 转录物，后者是通过体外转录制备的。使用改良的大肠杆菌与先前描述的核糖体相比，这些激活的抑制性 tRNA 能够将三种环状二肽并入二氢叶酸还原酶 (DHFR) 的 18 和 49 位。抑制产量随着内酰胺环大小的增加而增加，并且被发现以 3.4 到 8.9 的抑制产量进行5、6 和 7 元内酰胺二肽在两个不同蛋白质位点的百分比。7 元内酰胺更容易掺入，促使我们通过 1-乙基-3-(3-二甲氨基丙基)碳二亚胺 (EDCI) 介导的氨基酸环化制备两种 7 元环状酰肼（4和5），具有选择性在其侧链中保护肼官能团。与内酰胺二肽、酰肼二肽4 相同和5可用于激活相同的抑制性 tRNA 转录本并将环状二肽整合到
• Invention of MK-7845, a SARS-CoV-2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic
  作者：Valerie W. Shurtleff、Mark E. Layton、Craig A. Parish、James J. Perkins、John D. Schreier、Yunyi Wang、Gregory C. Adam、Nadine Alvarez、Soheila Bahmanjah、Carolyn M. Bahnck-Teets、Christopher W. Boyce、Christine Burlein、Tamara D. Cabalu、Brian T. Campbell、Steven S. Carroll、Wonsuk Chang、Manuel de Lera Ruiz、Enriko Dolgov、John F. Fay、Nicholas G. Fox、Shih Lin Goh、Timothy J. Hartingh、Danielle M. Hurzy、Michael J. Kelly、Daniel J. Klein、Franca-Maria Klingler、Harini Krishnamurthy、Shalley Kudalkar、Todd W. Mayhood、Philip M. McKenna、Edward M. Murray、Debbie Nahas、Christopher C. Nawrat、Steven Park、Dongming Qian、Anthony J. Roecker、Vijeta Sharma、William D. Shipe、Jing Su、Robert V. Taggart、Quang Truong、Yin Wu、Xiaoyan Zhou、Ningning Zhuang、David S. Perlin、David B. Olsen、John A. Howe、John A. McCauley

  DOI：10.1021/acs.jmedchem.3c02248

  日期：2024.3.14

  needed to complement vaccines. The virus’s main protease, 3CLPro, is an attractive drug target in part because it recognizes a unique cleavage site, which features a glutamine residue at the P1 position and is not utilized by human proteases. Herein, we report the invention of MK-7845, a novel reversible covalent 3CLPro inhibitor. While most covalent inhibitors of SARS-CoV-2 3CLPro reported to date contain

  随着 SARS-CoV-2 继续传播，需要抗病毒治疗来补充疫苗。该病毒的主要蛋白酶 3CLPro 是一个有吸引力的药物靶点，部分原因是它识别独特的切割位点，该切割位点在 P1 位点具有谷氨酰胺残基，并且不被人类蛋白酶利用。在此，我们报告了MK-7845的发明，这是一种新型可逆共价3CLPro抑制剂。虽然迄今为止报道的大多数 SARS-CoV-2 3CLPro 共价抑制剂在 P1 处含有酰胺作为 Gln 模拟物，但 MK-7845 在该位置带有二氟丁基取代基。 SAR 分析和 X 射线晶体学研究表明，该基团与 His163 相互作用，His163 与通常在 P1 处发现的酰胺取代基形成氢键的残基相同。除了具有良好的体内功效和可接受的预计人体剂量以及未增强的药代动力学之外，MK-7845 还表现出良好的溶解度和吸收特性，这可能归因于不常见的二氟丁基取代基。
• A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics
  作者：Magdalini Nasopoulou、Dimitris Georgiadis、Magdalini Matziari、Vincent Dive、Athanasios Yiotakis

  DOI：10.1021/jo071081l

  日期：2007.9.1

  [GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.