(R)-norphenylephrine | 5596-07-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (R)-norphenylephrine
• 英文别名: (+)-Norphenylephrine；Norfenefrine, (R)-；3-[(1R)-2-amino-1-hydroxyethyl]phenol
• CAS: 5596-07-6
• 化学式: C₈H₁₁NO₂
• mdl: MFCD00012879
• 分子量: 153.181
• InChiKey: LRCXRAABFLIVAI-QMMMGPOBSA-N

物化性质

• 沸点：
  360.7±27.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-norphenylephrine 、 乙酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以0.13 g的产率得到[3-[(1R)-2-acetamido-1-acetyloxyethyl]phenyl] acetate
  参考文献：
  名称：

  Asymmetric Hydrogenation of α-Chloro Aromatic Ketones Catalyzed by η⁶-Arene/TsDPEN−Ruthenium(II) Complexes

  摘要：

  Asymmetric hydrogenation of various alpha-chloro aromatic ketones with Ru(OTf)(TsDPEN)(eta(6)-arene) (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) produces the chiral chlorohydrins in up to 98% ee. This reaction can be conducted even on a 206-g scale. The hydrogenation of an alpha-chloro ketone with a phenol moiety has been utilized for the synthesis of (R)-norphenylephrine without protection-deprotection operations.

  DOI：

  10.1021/ol062661s
• 作为产物：
  描述：

  2-chloro-1-(3-hydroxy phenyl)ethan-1-one 在 palladium on activated charcoal 、 Ru(OTf)[(S,S)-TsDPEN](η⁶-mesitylene) sodium azide 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~100.0 ℃ 、1.01 MPa 条件下， 反应 38.0h， 生成 (R)-norphenylephrine
  参考文献：
  名称：

  Asymmetric Hydrogenation of α-Chloro Aromatic Ketones Catalyzed by η⁶-Arene/TsDPEN−Ruthenium(II) Complexes

  摘要：

  Asymmetric hydrogenation of various alpha-chloro aromatic ketones with Ru(OTf)(TsDPEN)(eta(6)-arene) (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) produces the chiral chlorohydrins in up to 98% ee. This reaction can be conducted even on a 206-g scale. The hydrogenation of an alpha-chloro ketone with a phenol moiety has been utilized for the synthesis of (R)-norphenylephrine without protection-deprotection operations.

  DOI：

  10.1021/ol062661s

文献信息

• Pharmaceutically active pyrrolidine derivatives as bax inhibitors
  申请人：——

  公开号：US20030171309A1

  公开（公告）日：2003-09-11

  The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7>; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及新的取代吡咯烷衍生物的化学式(I)。所述化合物通常用作药用活性化合物。具体来说，化学式(I)的吡咯烷衍生物在治疗和/或预防神经退行性疾病、与多谷氨酸氨基酸序列相关的疾病、癫痫、缺血、不孕症、心血管疾病、肾脏缺氧、肝炎和艾滋病方面具有用处。所述吡咯烷衍生物显示出对细胞死亡促进子Bax和/或导致Bax激活途径的调节作用，最显著地是下调至抑制活性，并因此允许阻止细胞色素(c)的释放。本发明还涉及新的具有药用活性的取代吡咯烷衍生物，以及它们的制备方法，其中X选自O、S、CR<6>R<7>、NOR<6>、NNR<6>R<7>组成的群；A选自—(C═O)—、—(C═O)—O—、—C(═NH)—、—(C═O)—NH—、—(C═S)—NH、—SO2-、—SO2NH—；—CH2-；B是一个群—(C═O)—NR<8>R<9>或代表具有化学式(II)的杂环残基，其中Q是NR<10>、O或S；n是选自0、1或2的整数；Y、Z和E与它们连接的两个碳共同形成一个5-6成员芳香族或杂芳族环。
• Pharmaceutically active pyrrolidine derivatives
  申请人：——

  公开号：US20030212012A1

  公开（公告）日：2003-11-13

  The present invention is related to pyrrolidine derivatives of formula (I). Said 1 compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及式(I)的吡咯烷衍生物。所述化合物优选用作药用活性化合物。具体而言，式(I)的吡咯烷衍生物在治疗和/或预防早产、早产和痛经方面是有用的。特别是，本发明涉及显示出氧催产素受体显著调节作用，特别是拮抗剂活性的吡咯烷衍生物。更具体地，所述化合物在治疗和/或预防由氧催产素介导的疾病状态，包括早产、早产和痛经方面是有用的。本发明还涉及新型吡咯烷衍生物以及其制备方法，其中X从CR6R7、NOR6、NNR6R7组中选择；A从—(C═O)—、—(C═O)—O—、—C(═NH)—、—(C═O)—NH—、—(C═S)—NH、—SO22—、—SO2NH—、—CH2—中选择；B是一个群—(C═O)—NR8R9或表示具有式(a)的杂环残基，其中Q是NR10、O或S；n是选择的整数0、1或2；Y、Z和E与它们连接的2个碳一起形成一个5-6成员芳基或杂芳基环。
• A New Copper(I)–Tetrahydrosalen-Catalyzed Asymmetric Henry Reaction and Its Extension to the Synthesis of (S)-Norphenylephrine
  作者：Yan Xiong、Fei Wang、Xiao Huang、Yuehong Wen、Xiaoming Feng

  DOI：10.1002/chem.200601262

  日期：2007.1.12

  A new chiral hydrogenated salen catalyst has been developed for the asymmetric Henry reaction which produces the expected products in moderate to high yields (up to 98 %) with excellent enantioselectivities (up to 96 % ee). A variety of aromatic, heteroaromatic, enal, and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 1 f (10 mol %), (CuOTf)(2)C(7)H(8)

  已开发出一种用于不对称亨利反应的新型手性氢化塞伦催化剂，该催化剂能以中等至高产率（高达98％）产生预期的产物，并具有出色的对映选择性（高达96％ee）。发现存在氢化的salen 1f（10 mol％），（CuOTf）（2）C（7）H（8）（5 mol％）的情况下，各种芳香族，杂芳香族，烯醛和脂肪族醛都是合适的底物）和4 A分子筛。该方法是耐空气的，并且容易使用容易获得的试剂进行操作，并且已经成功地扩展到以商业上可得的间羟基苯甲醛为原料，以67％的总产率合成（S）-去氧肾上腺素。根据实验研究和MM +计算，
• Studies on the syntheses of heterocyclie compounds. Part DXXVII.. the absolute configuration of 1,2,3,4-tetrahydro-1-phenylisoquinolines
  作者：Tetsuji Kametani、Shiroshi Shibuya、Hideo Sugi、Keiichiro Fukumoto

  DOI：10.1002/jhet.5570100405

  日期：1973.8

  The absolute configuraiton at the C1-position of 1,2,3,4-tetrahydro-1-phenylisoquinolines can be deduced from the CD curves of either the free base or its methiodide. Furthermore, the absolute con figuration of (+)-2-amino-1-(3-hydroxyphenyl)ethanol (V) was revised and found to have R-configuration at the C1 -position.

  1,2,3,4-四氢-1-苯基异喹啉在C 1位的绝对构型可以从游离碱或其甲硫酮的CD曲线推导出。此外，对（+）-2-氨基-1-（3-羟基苯基）乙醇（V）的绝对构型进行了修改，发现其在C 1-位具有R-构型。
• [EN] PHARMACEUTICALLY ACTIVE PYRROLIDINE DERIVATIVES AS BAX INHIBITORS<br/>[FR] DERIVES DE LA PYRROLIDINE PHARMACEUTIQUEMENT ACTIFS COMME INHIBITEURS DE BAX
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2001074769A1

  公开（公告）日：2001-10-11

  The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating - up to an inhibitory - activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR?6R7, NOR6, NNR6R7¿; A is selected from the group consisting of -(C=O)-, -(C=O)-O-, -C(=NH)-, -(C=O)-NH-, -(C=S)-NH, -SO¿2?-, -SO2NH-; -CH2-; B is either a group -(C=O)-NR?8R9¿ or represents a heterocyclic residue having the formula (II) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.

  本发明涉及公式（I）的新取代吡咯烷衍生物。所述化合物优选用作药物活性化合物。具体而言，公式（I）的吡咯烷衍生物在神经退行性疾病、与多谷氨酸重复序列相关的疾病、癫痫、缺血、不孕症、心血管疾病、肾脏缺氧、肝炎和艾滋病的治疗和/或预防中有用。所述吡咯烷衍生物显示出调节性，尤其是对于细胞死亡促进剂Bax和/或导致Bax的激活途径具有下调至抑制性的活性，并因此允许阻止细胞色素（c）的释放。本发明还涉及新型药物活性取代吡咯烷衍生物以及其制备方法，其中X选自O，S，CR?6R7，NOR6，NNR6R7¿的群；A选自-(C=O)-，-(C=O)-O-，-C（=NH）-，-(C=O)-NH-，-(C=S)-NH，-SO¿2?，-SO2NH-；-CH2-；B是一个-(C=O)-NR?8R9¿基团或代表具有公式（II）的杂环残基，其中Q是NR10，O或S；n是选择的0、1或2的整数；Y、Z和E与它们所连接的2个碳一起形成一个5-6成员芳基或杂芳基环。