methyl (S)-3-hydroxy-4-methylvalerate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: methyl (S)-3-hydroxy-4-methylvalerate
• 英文别名: (S)-methyl 3-hydroxy-4-methylpentanoate；methyl 3-hydroxy-4-methylpentanoate；methyl (S)-3-hydroxy-4-methylpentanoate；Methyl(s)-3-hydroxy-4-methylpentanoate；methyl (3S)-3-hydroxy-4-methylpentanoate
• 化学式: C₇H₁₄O₃
• 分子量: 146.186
• InChiKey: HIUDWDUEXPJHRR-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• 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：

  methyl (S)-3-hydroxy-4-methylvalerate 在 Rh/Al₂O₃ N,N-二甲基丙烯基脲 、 lithium hydroxide 、 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， -78.0 ℃ 、482.64 kPa 条件下， 反应 24.0h， 生成 (2R,3R)-3-Hydroxy-4-methyl-2-(4-methyl-cyclohexylmethyl)-pentanoic 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：

  在 Raney nickel W-2 作用下， 以 丙酮 为溶剂， 反应 0.33h， 生成 methyl (S)-3-hydroxy-4-methylvalerate
  参考文献：
  名称：

  Efficient Enantioselective Synthesis of Methyl Esters of α-Unsubstituted β-Hydroxy Acids via Asymmetric Aldol-Type Addition of Chiral Boron Enolates of (Methylthio)acetic Acid to Aldehydes

  摘要：

  (甲硫基)乙酸的手性硼烯醇盐与各种醛进行aldol型加成反应，可以立体选择性地并以良好产率得到α-(甲硫基)-β-羟基酸。通过脱硫作用，可以将缩合加合物的甲酯转化为高对映体纯度的α-未取代-β-羟基酸的甲酯。使用(+)-2-蒎烯和(+)-3-蒎烯的衍生物作为手性诱导剂。aldol型加成的对映选择性和非对映选择性有效地受到烯醇盐α-位上的SMe基团和所用手性配体类型的控制。

  DOI：

  10.1055/s-1996-4365

文献信息

• Development of Chiral Spiro P-N-S Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of β-Alkyl-β-Ketoesters
  作者：Deng-Hui Bao、Hui-Ling Wu、Chao-Lun Liu、Jian-Hua Xie、Qi-Lin Zhou

  DOI：10.1002/anie.201502860

  日期：2015.7.20

  The chiral tridentate spiro P‐N‐S ligands (SpiroSAP) were developed, and their iridium complexes were prepared. Introduction of a 1,3‐dithiane moiety into the ligand resulted in a highly efficient chiral iridium catalyst for asymmetric hydrogenation of β‐alkyl‐β‐ketoesters, producing chiral β‐alkyl‐β‐hydroxyesters with excellent enantioselectivities (95–99.9 % ee) and turnover numbers of up to 355 000

  研发了手性三齿螺旋螺-N‐S配体（SpiroSAP），并制备了其铱配合物。在配体中引入1,3-二硫杂环丁烷部分产生了高效的手性铱催化剂，用于β-烷基-β-酮酸酯的不对称加氢，生成具有出色对映选择性（95-99.9％ee的手性β-烷基-β-羟基酯）），营业额高达355 000。
• Over 98% Optical Yield Achieved by a Heterogeneous Catalysis. Substrate Design and Analysis of Enantio-Differentiating Factors of Tartaric Acid-Modified Raney Nickel Hydrogenation
  作者：Takashi Sugimura、Satoshi Nakagawa、Akira Tai

  DOI：10.1246/bcsj.75.355

  日期：2002.2

  Tartaric acid-modified Raney nickel (TA-MRNi) is a chiral heterogeneous catalyst for the hydrogenation of prochiral ketones. An optical yield (OY) of 86% with methyl acetoacetate (1) as a substrate was improved to 94–96% by employing β-keto esters having a proper bulkiness at the γ -position. The γ -bulkiness effect contributes to a high intrinsic enantio-differentiating ability (factor-i) of the TA-MRNi catalysis. Through the study, we found the best substrate, γ -cyclopropyl-β-keto ester, the hydrogenation of which resulted in 98.6% OY. This further improvement in the OY was ascribed to a smaller contribution of non-enantio-differentiating hydrogenation (N-site catalysis) due to the substrate-specific activation of the enantio-differentiating hydrogenation by the chiral modifier. The OY of the hydrogenation of 1 was analyzed by comparing with well-behaved β-keto esters, and the contribution of the factor-i and the N-site to the OY value was evaluated to deduce the origin of the enantiodifferentiation.

  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。
• Highly enantioselective Ru-catalyzed hydrogenation of β-keto esters using electron-donating bis(trialkylphosphine) ligand-TangPhos
  作者：Chun-Jiang Wang、Haiyan Tao、Xumu Zhang

  DOI：10.1016/j.tetlet.2006.01.093

  日期：2006.3

  Highly electron-donating bis(trialkylphosphine) TangPhos and its corresponding ruthenium complexes provided high enantioselectivities for the hydrogenation of β-keto esters. Up to 99.8% and 99.5% ee have been achieved in hydrogenation of β-alkyl and β-aryl substituted β-keto esters, respectively. Asymmetric hydrogenation of ethyl 4-chloro acetoacetate in 98.2% ee is also reported.

  高度供电子的双（三烷基膦）TangPhos及其相应的钌配合物为β-酮酸酯的氢化提供了高对映选择性。在β-烷基和β-芳基取代的β-酮酯的氢化中，分别获得了高达99.8％和99.5％的ee。还报道了4-氯乙酰乙酸乙酯在98.2％ee中的不对称氢化。
• Enantioselective catalysis with a chiral, phosphane-containing PMO material
  作者：Tomohiro Seki、Kevin McEleney、Cathleen M. Crudden

  DOI：10.1039/c2cc31247f

  日期：——

  biphenylene-bridged siloxane precursor in the presence of surfactant templates to give periodic mesoporous organosilicas (PMOs) functionalized with BINAP. Complexation of ruthenium followed by asymmetric catalytic hydrogenation and asymmetric transfer hydrogenation were carried out, and demonstrated that high levels of activity and selectivity are achievable with the chiral material.

  制备了新颖的双三乙氧基甲硅烷基-BINAP单体，并在表面活性剂模板的存在下与联苯桥连的硅氧烷前体共缩合，得到了周期性的介孔有机硅（PMO），其被BINAP官能化。进行钌的络合，然后进行不对称的催化氢化和不对称的转移氢化，证明使用手性材料可以实现高水平的活性和选择性。
• Asymmetric hydrogenation by RuCl₂(R-Binap)(dmf)_n encapsulated in silica-based nanoreactors
  作者：Juan Peng、Xuefeng Wang、Xiaoming Zhang、Shiyang Bai、Yaopeng Zhao、Can Li、Qihua Yang

  DOI：10.1039/c4cy00228h

  日期：——

  RuCl₂-(R-Binap)(dmf)_n encapsulated in silica-based nanoreactors: a solid catalyst as a whole, but a homogeneous catalyst on the nanoscale.

  RuCl₂-(R-Binap)(dmf)_n被封装在基于硅的纳米反应器中：作为一个固体催化剂，但在纳米尺度上是一个均相催化剂。