ethyl 2-(((benzyloxy)carbonyl)amino)-3-hydroxy-3-methylbutanoate | 1353743-41-5

• 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: ethyl 2-(((benzyloxy)carbonyl)amino)-3-hydroxy-3-methylbutanoate
• 英文别名: N-Cbz-β-OHVal-OEt；Ethyl 3-hydroxy-3-methyl-2-(phenylmethoxycarbonylamino)butanoate
• CAS: 1353743-41-5
• 化学式: C₁₅H₂₁NO₅
• 分子量: 295.335
• InChiKey: FHOURYWGRGCVJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(((benzyloxy)carbonyl)amino)-3-hydroxy-3-methylbutanoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、3.79 MPa 条件下， 反应 18.0h， 生成 ethyl 2-amino-3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  Yaku'amide A的聚合全合成

  摘要：

  报道了抗癌肽天然产物yaku'amide A的全合成。它的β-叔羟基氨基酸是通过区域选择性氨基羟基化反应制备的，涉及手性甲磺氧基氨基甲酸酯试剂。E-和Z -ΔIle残基的立体特异性构建是通过具有抗脱水、叠氮化物还原和O→N酰基转移的单锅反应完成的。在此过程中烯烃异构化可忽略不计。这些方法为天然产物提供了一种高度收敛和有效的合成路线。

  DOI：

  10.1002/anie.202014238
• 作为产物：
  描述：

  3-甲基-2-丁烯酸乙酯 、 benzyl ((methylsulfonyl)oxy)carbamate 在 四氧化锇 、 (8alpha,9R)-10,11-二氢脱氧辛可宁-9-醇 作用下， 以 水 、 乙腈 为溶剂， 反应 100.17h， 以31%的产率得到ethyl 2-(((benzyloxy)carbonyl)amino)-3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  深入了解使用手性配体的无碱 OsO4 催化的氨基羟基化。

  摘要：

  描述了对 β,β-二取代烯酸酯进行 OsO4 催化的对映选择性无碱氨基羟基化的尝试。在标准手性配体存在下获得低产率和外消旋产物，这表明由于来自 Os 金属中心的氨基醇产物的缓慢水解而发生了“第二循环”过程。使用氨基醇配体获得的对映选择性（60:40 er）略有改善，为这一假设提供了支持。基于密度泛函理论计算，有人提出，缺乏显着的对映选择性是由于第二循环中没有手性配体的低能(3 + 2)氧代/亚氨基环加成过渡态，该过渡态胜过了第一循环中的质子分解作用。

  DOI：

  10.1016/j.tet.2019.01.018

文献信息

• Solid-phase synthesis of peptides containing bulky dehydroamino acids
  作者：Jintao Jiang、Shi Luo、Steven L. Castle

  DOI：10.1016/j.tetlet.2014.12.097

  日期：2015.6

  A method of incorporating bulky α,β-dehydroamino acids such as dehydrovaline and dehydroethylnorvaline into peptides via solid-phase peptide synthesis is reported. The key step involves ring opening of an azlactone (i.e., oxazolone) containing the dehydroamino acid by the amino group of a resin-bound peptide. The use of Alloc-protected azlactones was key to the success of the process.

  报道了通过固相肽合成将大的α，β-脱氢氨基酸如脱氢缬氨酸和脱氢乙基正缬氨酸掺入肽中的方法。关键步骤涉及通过树脂结合肽的氨基将含脱氢氨基酸的内酯（即恶唑酮）开环。使用由Alloc保护的内酯是该方法成功的关键。
• [EN] SOLID-PHASE SYNTHESIS OF PEPTIDES CONTAINING BULKY DEHYDROAMINO ACIDS<br/>[FR] SYNTHÈSE EN PHASE SOLIDE DE PEPTIDES CONTENANT DES DÉHYDROAMINO ACIDES VOLUMINEUX
  申请人：CASTLE STEVEN L

  公开号：WO2016090305A1

  公开（公告）日：2016-06-09

  Methods of incorporating bulky α,β-dehydroamino acids such as dehydrovaline and dehydroethylnorvaline into peptides via solid-phase peptide synthesis and the resulting peptide compositions is reported. The synthesis method involves using azlactone intermediates for coupling with resin bound peptides.

  报道了将体积庞大的α，β-脱氢氨基酸（如脱氢缬氨酸和脱氢乙基缬氨酸）通过固相肽合成方法引入到肽链中，并得到的肽组成。合成方法涉及使用乳酸内酰胺中间体与固相肽偶联。
• Insights into base-free OsO4-catalyzed aminohydroxylations employing chiral ligands
  作者：Joseph M. Cardon、James C. Coombs、Daniel H. Ess、Steven L. Castle

  DOI：10.1016/j.tet.2019.01.018

  日期：2019.2

  process due to slow hydrolysis of the amino alcohol product from the Os metal center. Support for this hypothesis was provided by the slightly improved enantioselectivity (60:40 er) obtained with an amino alcohol ligand. Based on density functional theory calculations, it is proposed that the lack of significant enantioselectivity is due to a low-energy (3 + 2) oxo/imido cycloaddition transition state without

  描述了对 β,β-二取代烯酸酯进行 OsO4 催化的对映选择性无碱氨基羟基化的尝试。在标准手性配体存在下获得低产率和外消旋产物，这表明由于来自 Os 金属中心的氨基醇产物的缓慢水解而发生了“第二循环”过程。使用氨基醇配体获得的对映选择性（60:40 er）略有改善，为这一假设提供了支持。基于密度泛函理论计算，有人提出，缺乏显着的对映选择性是由于第二循环中没有手性配体的低能(3 + 2)氧代/亚氨基环加成过渡态，该过渡态胜过了第一循环中的质子分解作用。
• Impact of Dehydroamino Acids on the Structure and Stability of Incipient 3₁₀-Helical Peptides
  作者：Daniel Joaquin、Michael A. Lee、David W. Kastner、Jatinder Singh、Shardon T. Morrill、Gracie Damstedt、Steven L. Castle

  DOI：10.1021/acs.joc.9b02747

  日期：2020.2.7

  A comparative study of the impact of small, medium-sized, and bulky alpha,beta-dehydroamino acids (Delta AAs) on the structure and stability of Balarams incipient 3(10)-helical peptide (1) is reported. Replacement of the N-terminal Aib residue of 1 with a Delta AA afforded peptides 2a-c that maintained the 3(10)-helical shape of 1. In contrast, installation of a Delta AA in place of Aib-3 yielded peptides 3a-c that preferred a beta-sheet-like conformation. The impact of the Delta AA on peptide structure was independent of size, with small (Delta Ala), medium-sized (Z-Delta Abu), and bulky (Delta Val) Delta AAs exerting similar effects. The proteolytic stabilities of 1 and its analogs were determined by incubation with Pronase. Z-Delta Abu and Delta Val increased the resistance of peptides to proteolysis when incorporated at the 3-position and had negligible impact on stability when placed at the 1-position, whereas Delta Ala-containing peptides degraded rapidly regardless of position. Exposure of peptides 2a-c and 3a-c to the reactive thiol cysteamine revealed that Delta Ala-containing peptides underwent conjugate addition at room temperature, while Z-Delta Abu- and Delta Val-containing peptides were inert even at elevated temperatures. These results suggest that both bulky and more accessible medium-sized Delta AAs should be valuable tools for bestowing rigidity and proteolytic stability on bioactive peptides.
• Regioselective Base-Free Intermolecular Aminohydroxylations of Hindered and Functionalized Alkenes
  作者：Zhiwei Ma、Bradley C. Naylor、Brad M. Loertscher、Danny D. Hafen、Jasmine M. Li、Steven L. Castle

  DOI：10.1021/jo202375a

  日期：2012.1.20

  Regioselective base-free intermolecular aminohydroxylations of functionalized trisubstituted and 1,1-disubstituted alkenes employing benzoyloxycarbamate 3a and catalytic OsO4 are described. In all cases, the more substituted alcohol isomer is favored. Sluggish reactions could be promoted by gentle heating, the use of amine ligands, or increased catalyst loadings. A competitive rearrangement was observed with a secondary allylic alcohol substrate. The adducts serve as useful precursors to dehydroamino acids.