tert-butyl (2R,3R,4S)-2-{[(tert-butyldiphenylsilyl)oxy]methyl}-3,4-dihydroxypyrrolidine-1-carboxylate | 852616-66-1

• 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: tert-butyl (2R,3R,4S)-2-{[(tert-butyldiphenylsilyl)oxy]methyl}-3,4-dihydroxypyrrolidine-1-carboxylate
• 英文别名: (2R,3R,4S)-N-tert-butyloxycarbonyl-3,4-dihydroxy-2-(tert-butyldiphenylsiloxymethyl)pyrrolidine；(2R,3R,4S)-N-tert-butoxycarbonyl-2-tert-butyldiphenylsilyloxymethyl-3,4-dihydroxypyrrolidine；tert-butyl (2R,3R,4S)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-3,4-dihydroxypyrrolidine-1-carboxylate
• CAS: 852616-66-1
• 化学式: C₂₆H₃₇NO₅Si
• 分子量: 471.669
• InChiKey: SZXJZKQJQYWJKQ-XPWALMASSA-N

物化性质

• 沸点：
  531.4±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,3R,4S)-2-{[(tert-butyldiphenylsilyl)oxy]methyl}-3,4-dihydroxypyrrolidine-1-carboxylate 在 盐酸 、 对甲苯磺酸 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 9.0h， 生成 1,4-二脱氧-1,4-亚氨基-D-核糖醇
  参考文献：
  名称：

  通过Sharpless环氧化和烯烃复分解对羟基吡咯烷的对映选择性合成

  摘要：

  本文描述了由对映体纯的2，3-环氧-戊-4-烯-1-醇5对映体选择性合成多羟基化的吡咯烷。可以通过Sharpless环氧化容易地以任何构型获得的环氧醇，经过烯丙基胺的区域选择性C-3开环，Boc保护和开环易位，得到脱氢吡咯衍生物7。从该关键中间体中，高浓度地制备了1,4-二脱氧-1,4-亚氨基-d-核糖醇（+）- 3和1,4-二脱氧-1,4-亚氨基-d-烯丙醇（+）- 4。产量。这些化合物的对映异构体可以从具有相反构型的环氧醇开始以相同的顺序获得。

  DOI：

  10.1016/j.tetasy.2006.12.023
• 作为产物：
  描述：

  N-Boc-反式-4-羟基-L-脯氨酸甲酯 在 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 四氧化锇 、 lithium aluminium tetrahydride 、 二苯基二硒醚 、 氧化-4-甲基吗啉一水合物 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 15.0h， 生成 tert-butyl (2R,3R,4S)-2-{[(tert-butyldiphenylsilyl)oxy]methyl}-3,4-dihydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of 3‘-Deoxy-3‘-difluoromethyl Azanucleosides from trans-4-Hydroxy-l-proline

  摘要：

  Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.

  DOI：

  10.1021/jo050057+

文献信息

• Design, Synthesis and Biological Evaluation of Isoxazole-Based CK1 Inhibitors Modified with Chiral Pyrrolidine Scaffolds
  作者：Andreas Luxenburger、Dorian Schmidt、Chiara Ianes、Christian Pichlo、Marc Krüger、Thorsten von Drathen、Elena Brunstein、Graeme Gainsford、Ulrich Baumann、Uwe Knippschild、Christian Peifer

  DOI：10.3390/molecules24050873

  日期：——

  In this study, we report on the modification of a 3,4-diaryl-isoxazole-based CK1 inhibitor with chiral pyrrolidine scaffolds to develop potent and selective CK1 inhibitors. The pharmacophore of the lead structure was extended towards the ribose pocket of the adenosine triphosphate (ATP) binding site driven by structure-based drug design. For an upscale compatible multigram synthesis of the functionalized

  在这项研究中，我们报告了手性吡咯烷支架对3,4-二芳基-异恶唑基CK1抑制剂的修饰，以开发有效的和选择性的CK1抑制剂。铅结构的药效基团向由基于结构的药物设计驱动的三磷酸腺苷（ATP）结合位点的核糖口袋延伸。对于功能化的吡咯烷支架的高档兼容多谱图合成，我们使用了从蛋氨酸开始的手性库合成途径。在激酶和细胞分析中对关键化合物的生物学评估表明，支架对活性和选择性具有显着影响，但是，手性部分的绝对构型仅对抑制活性表现出有限的影响。配体-CK1δ配合物的X射线晶体学分析证实了3,4-二芳基-异恶唑抑制剂的预期结合方式。出乎意料的是，原始化合物在共结晶过程中经历了自发的Pictet-Spengler环化反应，并带有微量甲醛，以形成高效的新配体。我们的数据表明手性“核糖样”吡咯烷支架具有令人感兴趣的修饰药理活性化合物的潜力。
• Synthesis of 3‘-Deoxy-3‘-difluoromethyl Azanucleosides from <i>trans</i>-4-Hydroxy-<scp>l</scp>-proline
  作者：Xiao-Long Qiu、Feng-Ling Qing

  DOI：10.1021/jo050057+

  日期：2005.5.1

  Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.
• Enantioselective synthesis of hydroxylated pyrrolidines via Sharpless epoxidation and olefin metathesis
  作者：Caterina Murruzzu、Antoni Riera

  DOI：10.1016/j.tetasy.2006.12.023

  日期：2007.1

  The enantioselective synthesis of polyhydroxylated pyrrolidines from enantiomerically pure 2,3-epoxy-pent-4-en-1-ol 5 is described herein. The epoxy alcohol, readily available in any configuration by Sharpless epoxidation, was submitted to regioselective C-3 ring-opening with allyl amine, Boc-protection and ring-closing metathesis to yield dehydropyrrole derivative 7. From this key intermediate, 1

  本文描述了由对映体纯的2，3-环氧-戊-4-烯-1-醇5对映体选择性合成多羟基化的吡咯烷。可以通过Sharpless环氧化容易地以任何构型获得的环氧醇，经过烯丙基胺的区域选择性C-3开环，Boc保护和开环易位，得到脱氢吡咯衍生物7。从该关键中间体中，高浓度地制备了1,4-二脱氧-1,4-亚氨基-d-核糖醇（+）- 3和1,4-二脱氧-1,4-亚氨基-d-烯丙醇（+）- 4。产量。这些化合物的对映异构体可以从具有相反构型的环氧醇开始以相同的顺序获得。