1-[N-(tert-butyloxycarbonyl)-(1S)-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane | 206191-45-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[N-(tert-butyloxycarbonyl)-(1S)-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane
• 英文别名: 1-[N-Tert-butoxycarbonyl-(1S)-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane；tert-butyl N-[(1S)-2-hydroxy-1-(4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl)ethyl]carbamate
• CAS: 206191-45-9
• 化学式: C₁₃H₂₃NO₆
• 分子量: 289.329
• InChiKey: BRQXNMWTCKDSEP-ALXWSUNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[N-(tert-butyloxycarbonyl)-(1S)-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane 在 草酰氯 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 2.25h， 生成 1-(N-tert-butyloxycarbonyl-(1S,2S)-1-amino-2-hydroxypropyl)-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane
  参考文献：
  名称：

  Stereoselective Synthesis of Threo and Erythro β-Hydroxy and β-Disubstituted-β-Hydroxy α-Amino Acids

  摘要：

  Optically pure N-protected serine aldehyde equivalents can be prepared by the protection of the carboxylic group of serine by a cyclic ortho ester. Alkylation of N-Cbz-, N-Fmoc- or N-Boc-protected serine with oxetane tosylate 1 or bromide 2 gives the corresponding oxetane esters 4a-c which can easily be converted to the cyclic ortho esters 5a-c. A variety of unusual threo beta-hydroxy amino acids have been synthesized by Grignard addition to these optically pure serine aldehyde equivalents. The erythro diastereomers can be obtained by oxidation of the initial three adduct followed by reduction with LiBH4. Also described is a general approach for the diastereoselective synthesis of optically pure beta,beta-dialkyl-beta-hydroxy alpha-amino acids. These highly substituted amino acids are prepared by a sequence of Grignard addition to the optically active serine aldehyde equivalent, followed by oxidation of the initial adduct, and a second Grignard addition to the resulting ketone. The hydroxy adduct is obtained with very high diastereoselectivity (84-96% de). All four diastereomers can be selectively synthesized by varying the order of the Grignard additions and the chirality of the initial synthon. Removal of the protecting groups can be effected in very mild conditions, giving excellent yields of highly substituted amino acids in high diastereomeric purity.

  DOI：

  10.1021/jo972294l
• 作为产物：
  描述：

  3-甲基-3-羟甲基氧杂环丁烷 在 TEA 、 三氟化硼乙醚 、 caesium carbonate 、 sodium iodide 作用下， 以 吡啶 为溶剂， 反应 56.0h， 生成 1-[N-(tert-butyloxycarbonyl)-(1S)-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane
  参考文献：
  名称：

  Stereoselective Synthesis of Threo and Erythro β-Hydroxy and β-Disubstituted-β-Hydroxy α-Amino Acids

  摘要：

  Optically pure N-protected serine aldehyde equivalents can be prepared by the protection of the carboxylic group of serine by a cyclic ortho ester. Alkylation of N-Cbz-, N-Fmoc- or N-Boc-protected serine with oxetane tosylate 1 or bromide 2 gives the corresponding oxetane esters 4a-c which can easily be converted to the cyclic ortho esters 5a-c. A variety of unusual threo beta-hydroxy amino acids have been synthesized by Grignard addition to these optically pure serine aldehyde equivalents. The erythro diastereomers can be obtained by oxidation of the initial three adduct followed by reduction with LiBH4. Also described is a general approach for the diastereoselective synthesis of optically pure beta,beta-dialkyl-beta-hydroxy alpha-amino acids. These highly substituted amino acids are prepared by a sequence of Grignard addition to the optically active serine aldehyde equivalent, followed by oxidation of the initial adduct, and a second Grignard addition to the resulting ketone. The hydroxy adduct is obtained with very high diastereoselectivity (84-96% de). All four diastereomers can be selectively synthesized by varying the order of the Grignard additions and the chirality of the initial synthon. Removal of the protecting groups can be effected in very mild conditions, giving excellent yields of highly substituted amino acids in high diastereomeric purity.

  DOI：

  10.1021/jo972294l

文献信息

• Total Synthesis of GE81112A: An Orthoester-Based Approach
  作者：Scherin Fayad、Ardalan Jafari、Sören M. M. Schuler、Michael Kurz、Oliver Plettenburg、Peter E. Hammann、Armin Bauer、Gerrit Jürjens、Christoph Pöverlein

  DOI：10.1021/acs.joc.3c00094

  日期：2023.5.5

  three naturally occurring tetrapeptides and synthetic derivatives, is evaluated as a potential lead structure for the development of a new antibacterial drug. Although the first total synthesis of GE81112A reported by our group provided sufficient amounts of material for an initial in depth biological profiling of the compound, improvements of the routes toward the key building blocks were needed for

  GE81112系列由三种天然存在的四肽和合成衍生物组成，被评估为开发新抗菌药物的潜在先导结构。尽管我们小组报道的 GE81112A 的首次全合成为该化合物的初步深入生物分析提供了足够的材料，但需要改进关键构建模块的路线以进行进一步的升级和构效关系研究。确定的主要挑战是C合成中的立体选择性差-末端 β-羟基组氨酸中间体和 3-羟基哌啶酸的所有四种异构体的简明获取。在此，我们报告了 GE81112A 的第二代合成，这也适用于访问该系列的更多代表。基于Lajoie的原酸酯保护的丝氨酸醛作为关键构建块，所描述的路线既提供了β-羟基组氨酸中间体合成立体选择性的令人满意的改进，又提供了正交保护的顺式和反式-3-羟基哌啶酸的立体选择性方法。
• Stereoselective Synthesis of <i>Threo</i> and <i>Erythro</i> β-Hydroxy and β-Disubstituted-β-Hydroxy α-Amino Acids
  作者：Mark A. Blaskovich、Ghotas Evindar、Nicholas G. W. Rose、Scott Wilkinson、Yue Luo、Gilles A. Lajoie

  DOI：10.1021/jo972294l

  日期：1998.5.1

  Optically pure N-protected serine aldehyde equivalents can be prepared by the protection of the carboxylic group of serine by a cyclic ortho ester. Alkylation of N-Cbz-, N-Fmoc- or N-Boc-protected serine with oxetane tosylate 1 or bromide 2 gives the corresponding oxetane esters 4a-c which can easily be converted to the cyclic ortho esters 5a-c. A variety of unusual threo beta-hydroxy amino acids have been synthesized by Grignard addition to these optically pure serine aldehyde equivalents. The erythro diastereomers can be obtained by oxidation of the initial three adduct followed by reduction with LiBH4. Also described is a general approach for the diastereoselective synthesis of optically pure beta,beta-dialkyl-beta-hydroxy alpha-amino acids. These highly substituted amino acids are prepared by a sequence of Grignard addition to the optically active serine aldehyde equivalent, followed by oxidation of the initial adduct, and a second Grignard addition to the resulting ketone. The hydroxy adduct is obtained with very high diastereoselectivity (84-96% de). All four diastereomers can be selectively synthesized by varying the order of the Grignard additions and the chirality of the initial synthon. Removal of the protecting groups can be effected in very mild conditions, giving excellent yields of highly substituted amino acids in high diastereomeric purity.