(S)-methyl 3-cyclopropyl-3-hydroxypropanoate | 196793-00-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-methyl 3-cyclopropyl-3-hydroxypropanoate
• 英文别名: methyl (3S)-3-cyclopropyl-3-hydroxypropanoate
• CAS: 196793-00-7
• 化学式: C₇H₁₂O₃
• 分子量: 144.17
• InChiKey: AHZTZDNJDVAMPU-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-methyl 3-cyclopropyl-3-hydroxypropanoate 在 Rh/Al₂O₃ 吡啶 、 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 sodium hydroxide 、 氢气 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， -78.0~40.0 ℃ 、482.64 kPa 条件下， 反应 62.0h， 生成 (2R,3R)-2-(cyclohexylmethyl)-3-cyclopropyl-3-[formyl(tetrahydro-2H-pyran-2-yloxy)amino]propanoic acid
  参考文献：
  名称：

  Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)

  摘要：

  A program to improve upon the in vitro, in vivo, and physicochemical properties of N-hydroxyformamide TACE inhibitor GW 3333 (1) is described. Using the primary structure of pro-TNF-alpha, along with a homology model of the catalytic domain of TACE based on the X-ray diffraction coordinates of adamalysin, we synthesized N-hydroxyformamide TACE inhibitors containing a P2' arginine side chain. Introduction of nitro and sulfonyl electron-withdrawing groups covalently bound to the P2' guanidine moiety rendered the inhibitors electronically neutral at cellular pH and led to potent inhibition of TNF-alpha release from stimulated macrophages. Inhibitors containing these arginine mimetics were found to have increased solubility in simulated gastric fluid (SGF) relative to 1, allowing for the incorporation of lipophilic P1' side chains which had the effect of retaining potent TACE inhibition, but reducing potency against matrix metalloproteases (MMPs) thus increasing overall selectivity against MMP1, MMP3, and MMP9. Selected compounds showed good to excellent in vivo TNF inhibition when administered via subcutaneous injection. One inhibitor, 28a, with roughly 10x selectivity over MMPI and MMP3 and high solubility in SGF, was evaluated in the rat zymosan-induced pleuisy model of inflammation and found to inhibit zymosan-stimulated pleural TNF-alpha elevation by 30%.

  DOI：

  10.1021/jm0102654
• 作为产物：
  描述：

  3-环丙基-3-氧代丙酸甲酯 在 镍 L-酒石酸 、 氢气 、 sodium bromide 作用下， 以 四氢呋喃 为溶剂， 60.0 ℃ 、100.0 MPa 条件下， 反应 44.0h， 生成 (S)-methyl 3-cyclopropyl-3-hydroxypropanoate
  参考文献：
  名称：

  Over 98% Optical Yield Achieved by a Heterogeneous Catalysis. Substrate Design and Analysis of Enantio-Differentiating Factors of Tartaric Acid-Modified Raney Nickel Hydrogenation

  摘要：

  酒石酸改性的Raney镍(TA-MRNi)是一种手性非均相催化剂，用于前手性酮的氢化反应。以乙酰乙酸甲酯(1)为底物，光学收率(OY)为86%，当采用在γ位置具有适当体积的β-酮酯时，OY提高至94-96%。γ体积效应有助于TA-MRNi催化剂具有高固有的手性区分能力(因子-i)。通过研究，我们发现最佳底物，即γ-环丙基-β-酮酯，其氢化反应的光学收率达到了98.6%。这一光学收率的进一步提升归因于底物特定的手性修饰剂激活手性区分氢化反应，从而减少了非手性区分氢化(N-位点催化)的贡献。通过与表现良好的β-酮酯进行比较，分析了1氢化反应的OY，并评估了因子-i和N-位点对OY值的贡献，从而推导出手性区分的起源。

  DOI：

  10.1246/bcsj.75.355

文献信息

• A Substrate Specific Chiral Modifier Activation on Enantio-differentiating Hydrogenation over Tartaric Acid-Modified Raney Nickel
  作者：Satoshi Nakagawa、Takashi Sugimura、Akira Tai

  DOI：10.1246/cl.1998.1257

  日期：1998.12

  A comparative study of the reactivities of the hydrogenation of β-ketoesters over tartaric acid-modified and unmodified Raney nickels indicated that a substrate specific activation by the tartaric acid modification is the reason for the almost perfect enantio-differentiation in the reaction of methyl 3-cyclopropyl-3-oxopropanoate (4).

  对比研究显示，酒石酸改性与未改性Raney镍催化的β-酮酯氢化反应的反应性表明，酒石酸改性所导致的底物特异性活化是导致甲基3-环丙基-3-氧基丙酸酯（4）反应中几乎完美的手性差异化的原因。
• Almost Perfect Enantio-differentiating Hydrogenation of Methyl 3-Cyclopropyl-3-oxopropanoate over Tartaric Acid Modified Raney Nickel Catalyst
  作者：Satoshi Nakagawa、Takashi Sugimura、Akira Tai

  DOI：10.1246/cl.1997.859

  日期：1997.9

  Almost perfect enantio-differentiating hydrogenation was achieved by asymmetrically modified heterogeneous catalyst. The hydrogenation of methyl 3-cyclopropyl-3-oxopropanoate over tartaric acid modified Raney nickel gave methyl 3-cyclopropyl-3-hydroxypropanoate in more than 98% of optical purity.

  通过不对称改性的多相催化剂实现了几乎完美的对映异构氢化。3-环丙基-3-氧代丙酸甲酯在酒石酸改性的阮内镍上加氢得到光学纯度超过 98% 的 3-环丙基-3-羟基丙酸甲酯。