cis-1-(tert-butoxycarbonyl)-4-hydroxypiperidine-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: cis-1-(tert-butoxycarbonyl)-4-hydroxypiperidine-3-carboxylic acid
• 英文别名: (3S,4R)-1-(tert-Butoxycarbonyl)-4-hydroxypiperidine-3-carboxylic acid；(3S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid
• 化学式: C₁₁H₁₉NO₅
• 分子量: 245.276
• InChiKey: MZOSQXSHAOWJQY-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  cis-1-(tert-butoxycarbonyl)-4-hydroxypiperidine-3-carboxylic acid 在 dimethyl sulfide borane 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.33h， 生成
  参考文献：
  名称：

  通过抑制Gli介导的转录起作用的新型大环刺猬通路抑制剂的发现。

  摘要：

  通过载有两个侧基取代基的4,5-二氢-2 H-苯并[ b ] [1,5]恶唑啉-6（3 H）-一个核心的热门文献5进行了系统的药物化学研究结合N原子行走或环行走以及中心环扩展或提取方法的双环骨架结构，产生了一系列结构上独特的三环化合物。在这些化合物中，化合物29a被确定为对Hedgehog（Hh）信号通路最有效的化合物，IC 50值为23 nM。机制研究表明，化合物29a通过抑制转录因子Gli的表达而不是通过中断Gli与DNA的结合来抑制Hh信号通路。我们进一步观察到29a对Smo野生型和两个主要抗性突变体（Smo D473H和Smo W535L）均具有同等效力。在ptch±; p53 – / –髓母细胞瘤同种异体移植小鼠模型中，它有效抑制了髓母细胞瘤细胞的增殖并显示出显着的肿瘤生长抑制作用。尽管需要更多的研究来阐明29a与Gli的精确相互作用模式，但其有希望的体外和体内特性鼓励其作为新一

  DOI：

  10.1021/acs.jmedchem.7b01185
• 作为产物：
  描述：

  盐酸-4-哌啶酮-3-羧酸乙酯 在 lithium hydroxide 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 26.5h， 生成 cis-1-(tert-butoxycarbonyl)-4-hydroxypiperidine-3-carboxylic acid
  参考文献：
  名称：

  A Study of Baker's Yeast Reduction of Piperidone-carboxylates.

  摘要：

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.

  DOI：

  10.3891/acta.chem.scand.52-0461

文献信息

• Combinatorial chemistry of piperidine based carbohydrate mimics
  作者：Elisabeth Byrgesen、John Nielsen、Marianne Willert、Mikael Bols

  DOI：10.1016/s0040-4039(97)01249-5

  日期：1997.8

  the latter obtained from bakers yeast reduction of the corresponding piperidone, were coupled in solid-phase synthesis to form simplified oligosaccharide analogues. A split-and-mix synthesis approach was used to create small combinatorial libraries which were characterised by LC-MS and screened as inhibitors of glycosidases.

  哌啶羧酸和4-羟基哌啶-3-羧酸，后者是从面包酵母还原相应哌啶酮而获得的，它们在固相合成中偶联形成简化的寡糖类似物。使用拆分混合合成方法来创建小的组合文库，该文库以LC-MS为特征，并筛选为糖苷酶抑制剂。
• Nickel Catalysis via S_H2 Homolytic Substitution: The Double Decarboxylative Cross-Coupling of Aliphatic Acids
  作者：Artem V. Tsymbal、Lorenzo Delarue Bizzini、David W. C. MacMillan

  DOI：10.1021/jacs.2c08989

  日期：2022.11.23

  generation, radical sorting via selective binding to a Ni(II) center, and bimolecular homolytic substitution (SH2) at a high-valent nickel–alkyl complex. This catalytic manifold enables the hitherto elusive cross-coupling of diverse aliphatic carboxylic acids to generate valuable C(sp3)–C(sp3)-products. Notably, the powerful SH2 mechanism provides general access to sterically encumbered quaternary carbon

  交叉偶联平台传统上是围绕一系列闭壳步骤构建的，例如氧化加成、金属转移和还原消除。在此，我们描述了一种双光/镍催化歧管，它通过互补序列进行交叉偶联，涉及自由基生成、通过选择性结合到 Ni(II) 中心的自由基分选以及高催化下的双分子均解取代 (S H 2)。 -价镍-烷基络合物。这种催化歧管能够实现迄今为止难以捉摸的不同脂肪族羧酸的交叉偶联，生成有价值的 C(sp 3 )–C(sp 3 )-产物。值得注意的是，强大的 S H 2 机制提供了对空间阻碍的季碳中心的普遍访问，解决了片段偶联化学中长期存在的挑战。
• Discovery of Novel Macrocyclic Hedgehog Pathway Inhibitors Acting by Suppressing the Gli-Mediated Transcription
  作者：Gang Liu、Wenjing Huang、Juan Wang、Xiaohua Liu、Jun Yang、Yu Zhang、Yong Geng、Wenfu Tan、Ao Zhang

  DOI：10.1021/acs.jmedchem.7b01185

  日期：2017.10.12

  several series of structurally unique tricyclic compounds. Among these, compound 29a was identified as the most potent against the Hedgehog (Hh) signaling pathway showing an IC50 value of 23 nM. Mechanism studies indicated that compound 29a inhibited the Hh signaling pathway by suppressing the expression of the transcriptional factors Gli rather than by interrupting the binding of Gli with DNA. We further

  通过载有两个侧基取代基的4,5-二氢-2 H-苯并[ b ] [1,5]恶唑啉-6（3 H）-一个核心的热门文献5进行了系统的药物化学研究结合N原子行走或环行走以及中心环扩展或提取方法的双环骨架结构，产生了一系列结构上独特的三环化合物。在这些化合物中，化合物29a被确定为对Hedgehog（Hh）信号通路最有效的化合物，IC 50值为23 nM。机制研究表明，化合物29a通过抑制转录因子Gli的表达而不是通过中断Gli与DNA的结合来抑制Hh信号通路。我们进一步观察到29a对Smo野生型和两个主要抗性突变体（Smo D473H和Smo W535L）均具有同等效力。在ptch±; p53 – / –髓母细胞瘤同种异体移植小鼠模型中，它有效抑制了髓母细胞瘤细胞的增殖并显示出显着的肿瘤生长抑制作用。尽管需要更多的研究来阐明29a与Gli的精确相互作用模式，但其有希望的体外和体内特性鼓励其作为新一
• A Study of Baker's Yeast Reduction of Piperidone-carboxylates.
  作者：Marianne Willert、Mikael Bols、Anders Hjelholt Pedersen、Palle Schneider、Louisa Barré、Ole Hammerich、Inger Søtofte、Bengt Långström

  DOI：10.3891/acta.chem.scand.52-0461

  日期：——

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.