<2S-<2R*,α(R*),β(S*)>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid methyl ester | 133120-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: <2S-<2R*,α(R*),β(S*)>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid methyl ester
• 英文别名: tert-butyl (2S)-2-[(1R,2S)-1-hydroxy-3-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate
• CAS: 133120-85-1
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: YESVEVMVKPHDFA-GARJFASQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <2S-<2R*,α(R*),β(S*)>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid methyl ester 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 (1R,2S,8S)-hexahydro-1-hydroxy-2-methyl-3H-pyrrolizin-3-one
  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：

  (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 palladium on activated charcoal 三乙烯二胺 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 120.0h， 生成 <2S-<2R*,α(R*),β(S*)>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-hydroxy-α-methyl-2-pyrrolidinepropanoic acid methyl ester
  参考文献：
  名称：

  通过Baylis-Hillman反应轻松且立体选择性地合成N -Boc-dolaproine

  摘要：

  在本通讯中，我们报告了N -Boc-多拉脯氨酸（Dap）（一种抗肿瘤五肽Dolastatin 10的氨基酸残基）的立体选择性全合成。我们的策略基于N -Boc-脯氨酸和丙烯酸甲酯之间的Baylis-Hillman反应，然后进行非对映选择性的双键加氢和酯官能团的水解。

  DOI：

  10.1016/s0040-4039(02)02765-x

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。
• The Dolastatins. 17. Synthesis of Dolaproine and Related Diastereoisomers
  作者：George R. Pettit、Sheo Bux Singh、Delbert L. Herald、Paul Lloyd-Williams、Darko Kantoci、Douglas D. Burkett、Jozsef Barkoczy、Fiona Hogan、Terah R. Wardlaw

  DOI：10.1021/jo00100a034

  日期：1994.10

  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.
• An easy and stereoselective synthesis of N-Boc-dolaproine via the Baylis–Hillman reaction
  作者：Wanda P. Almeida、Fernando Coelho

  DOI：10.1016/s0040-4039(02)02765-x

  日期：2003.1

  In this communication we report a stereoselective total synthesis of N-Boc-dolaproine (Dap), an amino acid residue of the antineoplastic pentapeptide Dolastatin 10. Our strategy is based on a Baylis–Hillman reaction between N-Boc-prolinal and methyl acrylate, followed by a diastereoselective double bond hydrogenation and hydrolysis of the ester function.

  在本通讯中，我们报告了N -Boc-多拉脯氨酸（Dap）（一种抗肿瘤五肽Dolastatin 10的氨基酸残基）的立体选择性全合成。我们的策略基于N -Boc-脯氨酸和丙烯酸甲酯之间的Baylis-Hillman反应，然后进行非对映选择性的双键加氢和酯官能团的水解。