methyl-3-hydroxy-4-phenylbutanoate | 312599-02-3

• 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-3-hydroxy-4-phenylbutanoate
• 英文别名: (R)-methyl 3-hydroxy-4-phenylbutanoate；methyl (3R)-3-hydroxy-4-phenylbutanoate
• CAS: 312599-02-3
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: KUWWVYHNMGLJKE-SNVBAGLBSA-N

物化性质

• 沸点：
  321.7±30.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 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-3-hydroxy-4-phenylbutanoate 在 锂硼氢 、 三乙酰氧基硼氢化钠 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 266.5h， 生成 (R)-2-(1'-benzyl-3,4-dihydrospiro[[2]benzopyran-1,4'-piperidin]-3-yl)ethanol
  参考文献：
  名称：

  脂肪酶催化的动力学拆分是合成具有2-苯并吡喃结构的对映体纯σ配体的关键步骤

  摘要：

  为了获得对映异构纯σ 1与2-苯并吡喃支架与对映体纯2-苯基乙醇衍生物（一个氧杂的Pictet-Spengler反应受体配体- [R ）- 4和（小号） - 4设想。使用Amano脂肪酶PS-C II和乙酸异丙烯酯在叔丁基甲基醚中的外消旋醇（±）-4的动力学拆分导致（R）-构型醇（R）-4的产率为42％，对映体过量99.6％。（S）-配置的酒精（S）-4通过天野脂肪酶PS-C II催化水解对映体富集的乙酸（S）-5（76.9％ee）并提供（S）-4，收率26％和99.7％ee。通过双（溴代苯甲酸酯）（R）-7的激子耦合CD光谱测定醇（R）-4的绝对构型。合成2-苯并吡喃2和3的下一个重要步骤是对映体纯醇（R）-4和（S）-4的Oxa-Pictet-Spengler反应与哌啶酮缩酮8和氯丙醛缩醛12。构象限制的螺环2-苯并吡喃2显示更高的σ 1比更灵活氨基乙基衍生物亲和力3。（R）和（R，R

  DOI：

  10.1016/j.bmc.2017.04.042
• 作为产物：
  描述：

  5-(1-hydroxy-2-phenylethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 pIJ₅₆₇₅ 、 Streptomyces coelicolor A₃⁽²⁾ strain CH₉₉₉ 、 乙酰氯 作用下， 以 甲醇 为溶剂， 反应 48.25h， 生成 methyl-3-hydroxy-4-phenylbutanoate
  参考文献：
  名称：

  Genetic Engineering ofStreptomyces coelicolor A3(2) for the Enantioselective Reduction of Unnaturalβ-Keto-Ester Substrates

  摘要：

  DOI：

  10.1002/(sici)1521-3773(20000103)39:1<224::aid-anie224>3.0.co;2-r

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。
• 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。
• Highly efficient asymmetric transfer hydrogenation of ketones in emulsions
  作者：Weiwei Wang、Zhiming Li、Wenbo Mu、Ling Su、Quanrui Wang

  DOI：10.1016/j.catcom.2009.12.002

  日期：2010.1

  Ru-TsDPEN (TsDPEN = N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine) catalyzed asymmetric transfer hydrogenation of ketones in emulsions is reported for the first time. The new protocol provides markedly enhanced activity and enantioselectivities (up to 99% ee) as compared with results when performed either in an aqueous medium or in common organic solvents.

  首次报道了Ru-TsDPEN（TsDPEN ＝  N-（对甲苯磺酰基）-1,2-二苯基乙二胺）催化的酮在酮中的不对称转移氢化。与在水性介质或普通有机溶剂中进行的结果相比，新方案提供了显着增强的活性和对映选择性（高达99％ee）。
• Chiral acetate enolate equivalent for the synthesis of β-hydroxy acids and esters: X-ray crystal structure of RR,SS-(η5-C5H5)Fe(CO)(PPh3)(COCH2CH(OH)CH2CH3)]
  作者：Stephen G. Davies、Isabelle M. Dordor-Hedgecock、Peter Warner、Richard H. Jones、Keith Prout

  DOI：10.1016/0022-328x(85)87369-1

  日期：1985.4

  The aluminium enolate derived from the iron acetyl complex [(η5-C5H5Fe(CO)(PPh3)COCH3], in contrast to the lithium enolate, undergoes highly stereoselective aldol reactions with aldehydes to generate RR,SS-β-hydroxyacyl complexes which on decomplexation liberate β-hydroxy acids or esters. Determination of the molecular structure of RR,SS-[η5-C5H5)Fe(CO)(PPh3)(COCH2CH(OH)CH2CH3] allowed assignment of

  从铁衍生乙酰复杂的烯醇化铝[（η 5 -C 5 H ^ 5的Fe（CO）（PPH 3）COCH 3 ]，在对比的烯醇化锂，与醛生成经受高立体选择性羟醛缩合反应RR，SS - β羟络合物解络上释放β羟基酸或酯的分子结构的测定。RR，SS - [η 5 -C 5 H ^ 5）的Fe（CO）（PPH 3）（COCH 2 CH（OH）CH 2 CH 3 ]允许分配新手性中心的相对构型。
• Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)
  作者：Michael H. Rabinowitz、Robert C. Andrews、J. David Becherer、D. Mark Bickett、Dulce G. Bubacz、James G. Conway、David J. Cowan、Micheal Gaul、Kimberly Glennon、Millard H. Lambert、M. Anthony Leesnitzer、Darryl L. McDougald、Marcia L. Moss、David L. Musso、Michele C. Rizzolio

  DOI：10.1021/jm0102654

  日期：2001.11.1

  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%.