(1R,2R,8S)-hexahydro-1-hydroxy-2-methyl-3H-pyrrolizin-3-one | 133565-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯里西啶类
• 英文名称: (1R,2R,8S)-hexahydro-1-hydroxy-2-methyl-3H-pyrrolizin-3-one
• 英文别名: (1R,2R,7aS)-1-Hydroxy-2-methylhexahydro-3H-pyrrolizin-3-one；(1R,2R,8S)-1-hydroxy-2-methyl-1,2,5,6,7,8-hexahydropyrrolizin-3-one
• CAS: 133565-40-9
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: XQWRXKSRLOQXNP-DSYKOEDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (2S,3R,2'S)-3-(N-tert-butoxycarbonyl-2'-pyrrolidinyl)-3-hydroxy-2-methylpropanoic acid 在 potassium carbonate 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 (1R,2R,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

文献信息

• Efficient stereoselective synthesis of dolastatin 10, an antineoplastic peptide from a sea hare
  作者：Yasumasa Hamada、Kyoko Hayashi、Takayuki Shioiri

  DOI：10.1016/s0040-4039(00)92123-3

  日期：1991.2

  The stereoselective and efficient synthetic route to dolastatin 10, an antineoplastic peptide from a sea hare, has been developed. Dolaproine, one of the unusual constituents, was prepared in a highly stereoselective manner by the Evans aldol methodology.

  已经开发了立体选择性和有效的合成途径，以合成来自海兔的抗肿瘤肽dolastatin 10。通过Evans aldol方法以高度立体选择性的方式制备了Dolaproine（一种不常见的成分）。
• Stereoselective synthesis of dolastatin 10 and its congeners
  作者：Takayuki Shioiri、Kyoko Hayashi、Yasumasa Hamada

  DOI：10.1016/s0040-4020(01)80547-0

  日期：1993.2

  Efficient synthesis of dolastatin 10 (1), a potent antitumor peptide from a sea hare Dolabella auricularia, has been achieved in a stereoselective manner. Trisnordolastatin 10 (2) and its C9-epimer (3) have also been synthesized.

  有效合成dolastatin 10（1），一种来自海兔Dolabella auricularia的有效抗肿瘤肽，以立体选择性方式实现。Trisnordolastatin 10（2）及其C 9-受体（3）也已合成。
• 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。
• An efficient route to the pyrrolizidine ring system via an N-acyl anion cyclisation process
  作者：Anthony Murray、George R. Proctor、P.John Murray

  DOI：10.1016/0040-4020(96)00049-x

  日期：1996.3

  An enantioselective route to the pyrrolizidine ring system has been developed which uses an N-acyl anion cyclisation reaction as the key step. This methodology has provided the natural pyrrolizidines (−)-(1R, 8S)-1-hydroxy-pyrrolizidine 7, (−)-pyrrolizidin-1-ene-3-one 9 and (±)-trachelanthamidine 14. Extension of the process to an N-propionyl substrate provides ready access to a series of 2-methyl

  已经开发了使用N-酰基阴离子环化反应作为关键步骤的对吡咯烷环系统的对映选择性途径。该方法学提供了天然吡咯烷核苷（-）-（1R，8S）-1-羟基-吡咯烷核苷7，（-）-吡咯并恶唑-1-烯-3-酮9和（±）-正邻苯二甲酰胺14。将该方法扩展至N-丙酰基底物使得可以容易地获得一系列2-甲基吡咯嗪核苷。
• An expeditious synthesis of dolastatin 10
  作者：Kiyoshi Tomioka、Motomu Kanai、Kenji Koga

  DOI：10.1016/s0040-4039(00)79932-1

  日期：1991.5

  Total synthesis of dolastatin 10 (1) was completed by developing an efficient synthesis of two key amino acid components, Dil (6) and Dap (11), and subsequent stepwise coupling of five amino acid components from C-terminal Doe.