<2S-<2R*<(R*),α(R*),β(R*)>>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid 2-hydroxy-1,2,2-triphenylethyl ester | 158111-33-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: <2S-<2R*<(R*),α(R*),β(R*)>>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid 2-hydroxy-1,2,2-triphenylethyl ester
• 英文别名: tert-butyl (2S)-2-[(1S,2S)-1-hydroxy-3-[(1S)-2-hydroxy-1,2,2-triphenylethoxy]-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate
• CAS: 158111-33-2
• 化学式: C₃₃H₃₉NO₆
• 分子量: 545.676
• InChiKey: XCIVGNFIVHNDKB-HPEBZSCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  <2S-<2R*<(R*),α(R*),β(R*)>>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid 2-hydroxy-1,2,2-triphenylethyl ester 在 palladium on activated charcoal Proton Sponge 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 84.0h， 生成 (2S,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸
  参考文献：
  名称：

  The Dolastatins. 17. Synthesis of Dolaproine and Related Diastereoisomers

  摘要：

  A special challenge in accomplishing the total synthesis of dolastatin 10(1) entailed deducing the absolute configuration of the new beta-methoxy-gamma-amino acid component dolaproine (2) as 2S,2'R,3'R and devising a stereoselective synthesis. Synthesis of this unusual (S)-proline-derived unit as its N-tert-butoxycarbonyl derivative (9b) and three stereoisomers (9a, 9c, 9d) has been summarized. The diastereoisomers were assembled by an aldol condensation between aldehyde 5, derived from (S)-proline, with chiral propionate 6, followed by methylation and cleavage of the chiral directing ester group by hydrogenolysis to afford methyl ethers 9a-d. The absolute stereochemistry of the diastereoisomers was determined by a combination of X-ray crystallographic analyses (of 9a and lactam 11b formed from isomer 7a) and high-field (400 MHz) NMR studies. By using each of these isomers in a series of dolastatin 10 syntheses the stereochemistry of the dolaproine (2) unit of natural (-)-dolastatin 10 (1) was shown to be 2S,2'R,3'R.

  DOI：

  10.1021/jo00100a034
• 作为产物：
  描述：

  L-扁桃酸甲酯 在 吡啶 、 正丁基锂 、 二异丙胺 、 magnesium bromide 作用下， 以 乙醚 为溶剂， 反应 31.0h， 生成 <2S-<2R*<(R*),α(R*),β(R*)>>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid 2-hydroxy-1,2,2-triphenylethyl ester
  参考文献：
  名称：

  The Dolastatins. 17. Synthesis of Dolaproine and Related Diastereoisomers

  摘要：

  A special challenge in accomplishing the total synthesis of dolastatin 10(1) entailed deducing the absolute configuration of the new beta-methoxy-gamma-amino acid component dolaproine (2) as 2S,2'R,3'R and devising a stereoselective synthesis. Synthesis of this unusual (S)-proline-derived unit as its N-tert-butoxycarbonyl derivative (9b) and three stereoisomers (9a, 9c, 9d) has been summarized. The diastereoisomers were assembled by an aldol condensation between aldehyde 5, derived from (S)-proline, with chiral propionate 6, followed by methylation and cleavage of the chiral directing ester group by hydrogenolysis to afford methyl ethers 9a-d. The absolute stereochemistry of the diastereoisomers was determined by a combination of X-ray crystallographic analyses (of 9a and lactam 11b formed from isomer 7a) and high-field (400 MHz) NMR studies. By using each of these isomers in a series of dolastatin 10 syntheses the stereochemistry of the dolaproine (2) unit of natural (-)-dolastatin 10 (1) was shown to be 2S,2'R,3'R.

  DOI：

  10.1021/jo00100a034

文献信息

• Stereochemical Assignments for All Four Isomers of Dolaproine via Lactam Formation
  作者：Xiao Shang、Minh Nguyen、Nathan Ihle

  DOI：10.1055/s-2007-990936

  日期：2007.12

  The stereochemistry of all four possible stereoisomers of dolaproine was established through the syntheses and spectral analyses of structurally rigid bicyclic lactams. In addition, discrepancies with an earlier report were discovered and corrections are provided.

  通过结构刚性双环内酰胺的合成和光谱分析，确定了多拉普罗所有四种可能的立体异构体的立体化学。此外，还发现了与先前报告的差异并提供了更正。