methyl (2S)-2-amino-5-methyl-2-(2-methylpropyl)hex-4-enoate | 145452-11-5

• 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-amino-5-methyl-2-(2-methylpropyl)hex-4-enoate
• CAS: 145452-11-5
• 化学式: C₁₂H₂₃NO₂
• 分子量: 213.32
• InChiKey: XJBIJGFQDRBVRX-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-amino-5-methyl-2-(2-methylpropyl)hex-4-enoate 在 sodium periodate 、 四氧化锇 、 双(三甲基硅烷基)氨基钾 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 氯仿 、 水 、 丙酮 、 甲苯 、 苯 为溶剂， 反应 77.67h， 生成 methyl (2S)-2-[(5S)-5-[(5S)-5-[(5S)-5-[(5S)-5-benzyl-4-oxo-5-(2-oxoethyl)-1H-pyrrol-3-yl]-5-(2-methylpropyl)-4-oxo-1H-pyrrol-3-yl]-5-(2-methylpropyl)-4-oxo-1H-pyrrol-3-yl]-4-oxo-5-propan-2-yl-1H-pyrrol-3-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate
  参考文献：
  名称：

  De Novo Design, Synthesis, and X-ray Crystal Structures of Pyrrolinone-Based .beta.-Strand Peptidomimetics

  摘要：

  The de novo design and synthesis of a novel non-peptide scaffolding for beta-strand/sheet mimics are described. The scaffold consists of repeating 3,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains. The iterative construction of the pyrrolinones exploits a highly efficient cyclization of metalloimines, the latter derived from C-terminal aldehydes and readily available alpha-substituted alpha-amino ester building blocks. As predicted by interactive computer modeling and confirmed by X-ray crystallography, the polypyrrolinones present the side chains and carbonyl hydrogen-bond accepters in a solid-state conformation which mimics polypeptide beta-sheets. Importantly, the enaminone NH protons form hydrogen bonds both intramolecularly, stabilizing the beta-strand conformation, and intermolecularly, promoting sheet formation. The presence or absence of the nitrogen protecting group controlled antiparallel versus parallel sheet formation.

  DOI：

  10.1021/ja00101a017
• 作为产物：
  描述：

  D-亮氨酸 在 四(三苯基膦)钯 sodium hydroxide 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 5,5-二甲基-1,3-环己二酮 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 416.5h， 生成 methyl (2S)-2-amino-5-methyl-2-(2-methylpropyl)hex-4-enoate
  参考文献：
  名称：

  An effective synthesis of scalemic 3,5,5-trisubstituted pyrrolin-4-ones

  摘要：

  A new two-step method employs the intramolecular cyclization of metalated imino esters for the construction of scalemic 3,5,5-trisubstituted pyrrolin-4-ones (4). The imino esters in turn derive from alpha-disubstituted amino acids, the latter readily available via a new protocol exploiting the enantioretentive alkylation of oxazolidinones.

  DOI：

  10.1016/s0040-4039(00)60058-8

文献信息

• A Second-Generation Synthesis of Polypyrrolinone Nonpeptidomimetics:  Prelude to the Synthesis of Polypyrrolinones on Solid Support
  作者：Amos B. Smith、Hu Liu、Ralph Hirschmann

  DOI：10.1021/ol0059293

  日期：2000.7.1

  [reaction: see text] A second-generation asymmetric synthesis of polypyrrolinones (3) has been achieved exploiting scalemic alpha-aminolactones (1) as building blocks. Imine formation between an appropriate lactone (1) and aldehyde (2), followed in turn by pyrrolinone ring construction promoted by KHMDS in the presence of 18-crown-6 and modified Swern oxidation furnished pyrrolinone aldehyde 3. This iterative

  [反应：见正文]利用垢型α-氨基内酯（1）作为结构单元，已经实现了第二代不对称合成的聚吡咯烷酮（3）。在适当的内酯（1）和醛（2）之间形成亚胺，然后依次在18-crown-6和修饰的Swern氧化作用下，由KHMDS促进吡咯烷酮环的构建，从而得到吡咯烷酮醛3。这种迭代，有效的三步法该方案为在固体载体上合成聚吡咯烷酮铺平了道路。
• Synthesis of Polypyrrolinones on Solid Support
  作者：Amos B. Smith、Hu Liu、Hiroyuki Okumura、David A. Favor、Ralph Hirschmann

  DOI：10.1021/ol005931u

  日期：2000.7.1

  see text] An efficient, three-step iterative synthesis of polypyrrolinones has been achieved on solid support, setting the stage for the construction of a wide variety of libraries based on the pyrrolinone scaffold. Central to the approach is an effective end-game sequence featuring pyrrolinone ring construction with traceless release from the solid support.

  [反应：见正文]在固相支持物上实现了高效，三步迭代的聚吡咯烷酮合成，为构建基于吡咯烷酮骨架的多种文库奠定了基础。该方法的核心是有效的最终操作序列，其特征是吡咯烷酮环的结构以及从固体支持物中无痕释放。
• Pyrrolinone-Based HIV Protease Inhibitors. Design, Synthesis, and Antiviral Activity: Evidence for Improved Transport
  作者：Amos B Smith、Ralph Hirschmann、Alexander Pasternak、Mark C. Guzman、Akihisa Yokoyama、Paul A. Sprengeler、Paul L. Darke、Emilio A. Emini、William A. Schleif

  DOI：10.1021/ja00150a011

  日期：1995.11

  Pyrrolinone-based peptidomimetics, the first mimics of beta-strands, are potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolinones) described herein proved to be more active in cellular antiviral assays compared with an analogous peptide-derived inhibitor even though they are less effective in inhibiting the isolated protease. These results suggest that pyrrolinone inhibitors offer better transport properties than the corresponding peptide-based peptidomimetics; we attribute this effect to decreased solvation of the mimetics. Structure-activity relationships for the pyrrolinones correlate well with those reported for related peptides, consistent with similar modes of binding.
• Design, synthesis, and crystal structure of a pyrrolinone-based peptidomimetic possessing the conformation of a .beta.-strand: potential application to the design of novel inhibitors of proteolytic enzymes
  作者：Amos B. Smith、Terence P. Keenan、Ryan C. Holcomb、Paul A. Sprengeler、Mark C. Guzman、John L. Wood、Patrick J. Carroll、Ralph Hirschmann

  DOI：10.1021/ja00052a093

  日期：1992.12
• De Novo Design, Synthesis, and X-ray Crystal Structures of Pyrrolinone-Based .beta.-Strand Peptidomimetics
  作者：Amos B. Smith、Mark C. Guzman、Paul A. Sprengeler、Terence P. Keenan、Ryan C. Holcomb、John L. Wood、Patrick J. Carroll、Ralph Hirschmann

  DOI：10.1021/ja00101a017

  日期：1994.11

  The de novo design and synthesis of a novel non-peptide scaffolding for beta-strand/sheet mimics are described. The scaffold consists of repeating 3,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains. The iterative construction of the pyrrolinones exploits a highly efficient cyclization of metalloimines, the latter derived from C-terminal aldehydes and readily available alpha-substituted alpha-amino ester building blocks. As predicted by interactive computer modeling and confirmed by X-ray crystallography, the polypyrrolinones present the side chains and carbonyl hydrogen-bond accepters in a solid-state conformation which mimics polypeptide beta-sheets. Importantly, the enaminone NH protons form hydrogen bonds both intramolecularly, stabilizing the beta-strand conformation, and intermolecularly, promoting sheet formation. The presence or absence of the nitrogen protecting group controlled antiparallel versus parallel sheet formation.