methyl (R)-2-cyclohexyl-2-hydroxy-2-phenylacetate | 20585-38-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (R)-2-cyclohexyl-2-hydroxy-2-phenylacetate
• 英文别名: methyl (R)-α-cyclohexyl-α-hydroxybenzeneacetate；methyl (R)-cyclohexylhydroxyphenylacetate；Methyl cyclohexylphenylglycolate, (-)-；methyl (2R)-2-cyclohexyl-2-hydroxy-2-phenylacetate
• CAS: 20585-38-0
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: SPTZOODMHSABLY-HNNXBMFYSA-N

物化性质

• 沸点：
  373.4±22.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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 (R)-2-cyclohexyl-2-hydroxy-2-phenylacetate 在 sodium hydroxide 作用下， 生成 (R)-环己基羟基苯乙酸
  参考文献：
  名称：

  不对称合成。第三部分 （R）-2-羟基-2-苯基丙酸，（R）-和（S）-2-环己基-2-羟基-2-苯基乙酸的立体定向合成。（R）（–）-2-羟基-2-苯基丙酸和（S）（+）-2-苯基丙酸之间的构型关系

  摘要：

  碳水化合物衍生物光子晶体（R）（OH）[CHOH] Ñ ·CH 2 ·OH含有已知绝对构型的不对称中心苄降解为简单酸类光子晶体（R）（OH）CO 2 H.的合成（- [R ）描述了-2-羟基-2-苯基丙酸和（R）-和（S）-2-环己基-2-羟基-2-苯基乙酸。（R）（-）-2-羟基-2-苯基丙酸和（S）（+）-2-苯基丙酸之间的构型关系是通过一种新颖的方法建立的。用Nmr光谱分析表明阮内镍可对6-脱氧-1,2- O-异亚丙基-5- C-苯基-β- L进行氢解-异呋喃糖立体定向地进行，并保留构型，并且产物降解为（S）（+）-2-苯基丙酸。

  DOI：

  10.1039/j39680001693
• 作为产物：
  描述：

  D-扁桃酸 在 palladium on activated charcoal 氢氧化钾 、 硫酸 、 氢气 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正戊烷 为溶剂， -80.0~-15.0 ℃ 、500.0 kPa 条件下， 反应 3.0h， 生成 methyl (R)-2-cyclohexyl-2-hydroxy-2-phenylacetate
  参考文献：
  名称：

  Stereoselective Synthesis and Biodistribution of Potent [¹¹C]-Labeled Antagonists for Positron Emission Tomography Imaging of Muscarinic Receptors in the Airways

  摘要：

  Quantitation of muscarinic receptors in the lungs in vivo with positron emission tomography (PET) is of clinical interest. For that purpose we decided to develop [C-11]-labeled ligands with a high affinity (K-D < 0.1 nM). Three quaternary muscarinic antagonists, racemic N-methylpiperidin-4-yl 2-cyclohexy-2-2-hydroxy-2-phenylacetate methiodide 1a (pK(B) = 10.39), its (R)-isomer 1b (pK(B) = 11.08), and (R,R)-quinuclidin-3-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 2 (pK(B) = 11.28), were labeled by reacting [C-11]CH3I With their tertiary amine precursors. The enantiomerically pure tertiary amine precursors were prepared by stereoselective synthesis starting from (R)-(-)-mandelic acid. In vitro binding assay of 1b and 2 demonstrated that both ligands bind with very high affinity to the muscarinic receptor subtypes M(1), M(2), and M(3). They are more potent than the muscarinic antagonist (R)-N-methylquinuclidinyl benzilate ((R)-MQNB). Distribution studies with la, 1b, and 2 in control and atropine-treated male Wistar rats demonstrated significant specific binding (90-99% of total issue uptake) in tissues containing cholinoceptors (heart, intestine, lung, pancreas, spleen, stomach, submandibular gland). Because the tissue/plasma concentration ratios of 1b are most favorable, this ligand was used for further evaluation. Analysis of plasma samples showed a very rapid clearance (t(1/2) = 0.3 min) of the radioligand 1b and a relatively slow appearance of a hydrophilic metabolite. At 15 min postinjection of 1b, analysis of heart, lungs, and liver showed that respectively 99%, 88%, and 8% of the tissue radioactivity corresponded with the parent compound. Ligand 1b appears to be an excellent candidate for PET studies of mAChR receptors in heart and lungs.

  DOI：

  10.1021/jm960374w

文献信息

• Treating urinary incontinence using (S)-desethyloxybutynin
  申请人：Sepracor, Inc.

  公开号：US05677346A1

  公开（公告）日：1997-10-14

  A method for treating urinary incontinence while avoiding concomitant liability of adverse effects associated with racemic oxybutynin is disclosed. The method comprises administering a therapeutically effective amount of (S)-oxybutynin, (S)-desethyloxybutynin or a pharmaceutically acceptable salt thereof, substantially free of the corresponding R enantiomer. Pharmaceutical compositions in the form of tablets and transdermal devices comprising (S)-oxybutynin or (S)-desethyloxybutynin and an acceptable carrier are also disclosed, as is a synthesis of desethyloxybutynin.

  揭示了一种治疗尿失禁的方法，同时避免了与左旋氧丁啉相关的不良效应的连带责任。该方法包括给予(S)-氧丁啉、(S)-去乙氧基氧丁啉或其药用可接受的盐的治疗有效量，基本上不含相应的R对映体。还公开了包含(S)-氧丁啉或(S)-去乙氧基氧丁啉和可接受载体的片剂和经皮设备的药物组合物，以及去乙氧基氧丁啉的合成方法。
• [EN] 3,4,6,7-TETRAHYDRO-1 H-PYRROLO[3,4-D]PYRIMIDINE-2,5-DIONES AND THEIR THERAPEUTIC USE<br/>[FR] 3,4,6,7-TÉTRAHYDRO-1H-PYRROLO[3,4-D]PYRIMIDINE-2,5-DIONES ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2009060203A1

  公开（公告）日：2009-05-14

  A compound of formula (IA) or (IB): wherein A is aryl or heteroaryl; D is oxygen or sulphur; R1, R2, R3 and R5 are independently each hydrogen, halogen, nitro, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, hydroxy or C1-C6-alkoxy or C2-C6- alkenyloxy,, wherein C1-C6-alkyl and C1-C6-alkoxy can be further substituted with one to three identical or different radicals selected from the group consisting of halogen, hydroxy and C1-C4-alkoxy; R4 is hydrogen CrC6-alkyl, formyl, aminocarbonyl, mono- or di-C1-C4- alkylaminocarbonyl, C3-C8-cycloalkylcarbonyl, C1-C6-alkylcarbonyl, C1-C6- alkoxycarbonyl, N-(C1-C4-alkylsulfonyl)-aminocarbonyl, N-(C1-C4-alkylsulfonyl)-N-(C1-C4-alkyl)-aminocarbonyl, heteroaryl, heterocycloalkyl, heteroarylcarbonyl or heterocycloalkylcarbonyl; wherein C1-C6-alkyl, mono- and di-C1-C4- alkylaminocarbonyl, C1-C6-alkylcarbonyl, C1-C2-alkoxycarbonyl, heteroaryl and heterocycloalkyl can be substituted with one to three identical or different radicals selected from the group consisting of aryl, heteroaryl, hydroxyl, C1-C4-alkoxy, hydroxycarbonyl, C1-C6-alkoxycarbonyl, aminocarbonyl, mono and di-C1-C4- alkylaminocarbonyl, amino, mono- and di-C1-C4-alkylamino, C1-C4- alkylcarbonylamino, cyano, N-(mono- and di-Ci-C4-alkylamino-d-C4-alkyl)- aminocarbonyl, N-(C1-C4-alkoxy-C1-C4-alkyl)-aminocarbonyl or halogen; -[Linker]- is a divalent linker radical; and M is a moiety having M3 receptor antagonist activity.

  式（IA）或（IB）的化合物：其中A是芳基或杂环芳基；D是氧或硫；R1、R2、R3和R5分别独立地是氢、卤素、硝基、氰基、C1-C6-烷基、C2-C6-烯基、C2-C6-炔基、羟基或C1-C6-烷氧基或C2-C6-烯氧基，其中C1-C6-烷基和C1-C6-烷氧基可以进一步被选择自卤素、羟基和C1-C4-烷氧基的相同或不同基团取代；R4是氢、CrC6-烷基、甲酰基、氨基甲酰基、单或双C1-C4-烷基氨基甲酰基、C3-C8-环烷基甲酰基、C1-C6-烷基甲酰基、C1-C6-烷氧基甲酰基、N-(C1-C4-烷基磺酰基)-氨基甲酰基、N-(C1-C4-烷基磺酰基)-N-(C1-C4-烷基)-氨基甲酰基、杂环芳基、杂环烷基、杂环芳基甲酰基或杂环烷基甲酰基；其中C1-C6-烷基、单和双C1-C4-烷基氨基甲酰基、C1-C6-烷基甲酰基、C1-C2-烷氧基甲酰基、杂环芳基和杂环烷基可以被选择自芳基、杂环芳基、羟基、C1-C4-烷氧基、羟基甲酰基、C1-C6-烷氧基甲酰基、氨基甲酰基、单和双C1-C4-烷基氨基甲酰基、氨基、单和双C1-C4-烷基胺基、C1-C4-烷基甲酰胺基、氰基、N-(单和双C1-C4-烷基胺基-d-C4-烷基)-氨基甲酰基、N-(C1-C4-烷氧基-C1-C4-烷基)-氨基甲酰基或卤素的相同或不同基团取代；-[连接物]-是二价连接物基团；M是具有M3受体拮抗活性的基团。
• Chiral Macrocyclic Catalysts for the Enantioselective Addition of Lithium Acetylides to Ketones
  作者：Kenji Yamashita、Yuji Tabata、Katsuya Yamakawa、Takuya Mochizuki、Kai Matsui、Manabu Hatano、Kazuaki Ishihara

  DOI：10.1021/jacs.3c08905

  日期：2023.12.6

  the preparation of versatile chiral alcohols that are widely found in pharmaceuticals and natural products. Although a variety of enantioselective variations have been reported, alkynyl addition to simple ketones remains an unmet challenge due to their low reactivity and difficult enantiofacial discrimination. Here, we report a method for the catalytic enantioselective addition of lithium acetylide

  羰基化合物上的炔基加成是制备广泛存在于药物和天然产物中的多功能手性醇的一种有价值的合成方法。尽管已经报道了多种对映选择性变化，但由于其低反应性和困难的对映面辨别，炔基加成到简单酮仍然是一个未解决的挑战。在这里，我们报告了一种使用大环联萘酸锂作为催化剂将乙炔锂催化对映选择性加成到各种酮上的方法。这些反应通常会受到锂物质容易聚集的影响，从而导致催化剂活性和选择性较低。本研究设计的大环结构可以防止这种聚集，提供单体和高活性催化剂，可以在 5-30 分钟内从各种酮提供对映体富集的叔醇。此外，大环化合物的有限空腔和亲脂性赋予系统底物特异性，表现出与酶促反应类似的多选择性。因此，这些发现为合理设计具有高水平反应性和多选择性的小分子人工酶提供了新的见解。
• Visser, T. J.; Wegman, T.; Waarde, A. van, Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 515 - 517
  作者：Visser, T. J.、Wegman, T.、Waarde, A. van、Doze, P.、Elsinga, P. H.、Vaalburg, W.

  DOI：——

  日期：——
• [EN] NEW CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES INÉDITS
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2008096127A2

  公开（公告）日：2008-08-14

  [EN] The present invention provides compounds of formula (I) having muscarinic M3 receptor and ß-adrenergic receptor modulating activity; processes for their preparation and their use in therapy; wherein A, R¹, R², R³ and R⁴ are defined herein.
  [FR] La présente invention concerne des composés de formule (I) possédant une activité en matière de modulation du récepteur muscarinique M3 et du récepteur ß-adrénergique ; des procédés de préparation de ceux-ci et leur utilisation à des fins thérapeutiques ; A, R¹, R², R³ et R⁴ étant comme défini dans les présentes.