(R)-octopamine | 876-04-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (R)-octopamine
• 英文别名: (R)-1-hydroxy-1-(4-hydroxyphenyl)-2-aminoethane；(-)-Octopamine；(R)-(-)-octopamine；(+)-octopamine；octopamine；(R)-2-amino-(4-hydroxyphenyl)ethanol；4-[(1R)-2-amino-1-hydroxyethyl]phenol
• CAS: 876-04-0
• 化学式: C₈H₁₁NO₂
• mdl: MFCD00012881
• 分子量: 153.181
• InChiKey: QHGUCRYDKWKLMG-QMMMGPOBSA-N

物化性质

• 比旋光度：
  D25 -56.0° (0.1N HCl); -37.4° (H2O)
• 物理描述：
  Solid
• 碰撞截面：
  147.3 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 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

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  奥克巴胺	octopamine	104-14-3	C8H11NO2	153.181
  (R)-2-(4-羟基苯基)-2-羟基乙腈	(R)-2-(4-hydroxyphenyl)-2-hydroxyacetonitrile	77943-99-8	C8H7NO2	149.149
  对羟基苯乙胺	tyrosamine	51-67-2	C8H11NO	137.181
  (R)-(-)-2-叠氮基-1-(4-苄氧基苯基)-1-乙醇	(R)-(-)-2-azido-1-(4-benzyloxyphenyl)-1-ethanol	473552-22-6	C15H15N3O2	269.303

反应信息

• 作为反应物：
  描述：

  (R)-octopamine 生成 4-[(1R)-2-[[(Z)-1-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethylamino]-2-nitroethenyl]amino]-1-hydroxyethyl]phenol
  参考文献：
  名称：

  HIRAI, SHIRO;HIRANO, HIROSHI;ARAI, HIROTOSHI;KIBA, YASUO;SHIBATA, HISANAR+

  摘要：

  DOI：
• 作为产物：
  描述：

  [(R)-2-hydroxy-2-(4-acetoxy-phenyl)-ethyl]-carbamic acid benzyl ester 在 palladium on activated charcoal 氢氧化钾 、 氢气 作用下， 以 乙醇 为溶剂， 20.0~25.0 ℃ 、101.33 kPa 条件下， 反应 9.0h， 生成 (R)-octopamine
  参考文献：
  名称：

  Identification from a Combinatorial Library of a Small Molecule that Selectively Induces Apoptosis in Cancer Cells

  摘要：

  The selective induction of death in cancer cells is a major challenge in modern medicine. In this communication we describe the synthesis of an 88-membered combinatorial library, and the subsequent evaluation of these compounds for their ability to selectively induce apoptosis in cancerous cells. A compound was identified from the library that induces apoptosis in U-937 and HL-60 cell lines. This compound is a remarkably selective pro-apoptotic agent for these cancer cell lines, as it does not induce significant death in noncancerous white blood cells, even at concentrations as high as 1000 muM.

  DOI：

  10.1021/ja038043d

文献信息

• Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
  作者：Inha Cho、Christopher K. Prier、Zhi‐Jun Jia、Ruijie K. Zhang、Tamás Görbe、Frances H. Arnold

  DOI：10.1002/anie.201812968

  日期：2019.3.4

  Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable

  从神经递质到抗病毒剂的生物活性化合物中广泛存在手性1,2-氨基醇。尽管已经开发出许多用于获得氨基醇的合成方法，但是烯烃直接氨基羟基化为未保护的，对映体富集的氨基醇仍然是一个挑战。使用定向进化，我们设计了一种基于热稳定细胞色素c的血红蛋白生物催化剂，该生物色素在厌氧条件下使用O将烯烃直接以高对映选择性（高达2500 TTN和90％ee）转化为氨基醇。新戊酰羟胺作为胺化剂。建议该反应通过在酶活性位点产生的反应性铁氮物种进行，从而可以通过蛋白质工程调节催化剂的活性和选择性。
• 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。
• Synthesis of Aromatic 1,2-Amino Alcohols Utilizing a Bienzymatic Dynamic Kinetic Asymmetric Transformation
  作者：Johannes Steinreiber、Martin Schürmann、Friso van Assema、Michael Wolberg、Kateryna Fesko、Christoph Reisinger、Daniel Mink、Herfried Griengl

  DOI：10.1002/adsc.200700051

  日期：2007.6.4

  The applicability of the recent published bienzymatic protocol for the synthesis of (R)-2-amino-1-phenylethanol was tested using L-threonine aldolase from Pseudomonas putida and l-tyrosine decarboxylase from either Enterococcus faecalis (Efa) or two genes from Enterococcus faecium (Efi1, Efi2). In all 21 benzaldehyde derivatives were applied for an initial TLC screening. On a small scale, octopamine

  对的（合成的最近出版bienzymatic协议的适用性- [R）-2-氨基-1-苯基-乙醇使用从L-苏氨酸醛缩酶试验恶臭假单胞菌和L-酪氨酸脱羧酶从任一粪肠球菌（EFA），或从两个基因肠球菌屎肠球菌（EFI1，EFI2）。在所有21种苯甲醛衍生物中均进行了初步TLC筛选。使用Efi1以小规模获得章鱼胺和去甲肾上腺素作为（S）-对映体。三种方案均按规模生产，可产生对映体富集的（S）-章鱼胺（产率99％，ee 81％），（R）-2-氨基-1-苯基乙醇（产率61％，ee62％）和（S）-去甲肾上腺素（收率76％，ee 79％）。
• Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia
  作者：Michele L. R. Heffernan、Lee W. Herman、Scott Brown、Philip G. Jones、Liming Shao、Michael C. Hewitt、John E. Campbell、Nina Dedic、Seth C. Hopkins、Kenneth S. Koblan、Linghong Xie

  DOI：10.1021/acsmedchemlett.1c00527

  日期：2022.1.13

  (SEP-363856) is a trace-amine associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity in Phase 3 clinical development, with FDA Breakthrough Therapy Designation, for the treatment of schizophrenia. TAAR1 is a G-protein-coupled receptor (GPCR) that is expressed in cortical, limbic, and midbrain monoaminergic regions. It is activated by endogenous trace amines, and is believed to play

  Ulotaront (SEP-363856) 是一种微量胺相关受体 1 (TAAR1) 激动剂，具有 5-HT1A 受体激动剂活性，处于 3 期临床开发阶段，获得 FDA 突破性治疗指定，用于治疗精神分裂症。TAAR1 是一种 G 蛋白偶联受体 (GPCR)，在皮质、边缘和中脑单胺能区域表达。它被内源性微量胺激活，并被认为在调节多巴胺能、5-羟色胺能和谷氨酸能回路中起重要作用。本文报道了 ulotaront 及其类似物与内源性 TAAR1 激动剂相比的 TAAR1 激动数据。此外，围绕 ulotaront 建立了人类 TAAR1 同源模型，以识别关键相互作用并试图更好地了解支架特异性 TAAR1 激动剂的结构-活性关系。