1-hydroxymethyl-tetrahydro-β-carboline | 21236-66-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-hydroxymethyl-tetrahydro-β-carboline
• 英文别名: 1-hydroxymethyl-1,2,3,4-tetahydro-β-carboline；1-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline；1-Hydroxymethyl-1,2,3,4-tetrahydro-norharman；(2,3,4,9-tetrahydro-1H-β-carbolin-1-yl)-methanol；(1RS)-1-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline；2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-ylmethanol
• CAS: 21236-66-8
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: NEPUCDWQTZIZIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  152 °C
• 沸点：
  431.5±40.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-hydroxymethyl-tetrahydro-β-carboline 在 sodium hydroxide 、 sodium acetate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 (S)-2-(6-Methoxy-naphthalen-2-yl)-propionic acid (R)-2-acetyl-2,3,4,9-tetrahydro-1H-β-carbolin-1-ylmethyl ester
  参考文献：
  名称：

  Unprecedented racemization of ( S )-(+)-naproxen during a BOP-mediated esterification. X-Ray structures of diastereomeric esters

  摘要：

  During esterification of enantiomerically pure (S)-(+)-naproxen under mild conditions with the use of the BOP-reagent, a complete racemization was observed. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00097-5
• 作为产物：
  描述：

  N-(2,2-diethoxyethyl)tryptamine 在 溶剂黄146 作用下， 以 水 为溶剂， 以24%的产率得到1-hydroxymethyl-tetrahydro-β-carboline
  参考文献：
  名称：

  新型杂环系统15-氮杂育亨宾的合成

  摘要：

  已经研究了两种合成途径来合成15-氮杂异戊二烯环系统。第一个是基于色胺和哌啶缩醛4之间的Pictet-Spengler缩合反应，产生的五环化合物2a的收率非常低。第二个更有效的途径涉及从酰亚胺11生成的N-酰亚胺阳离子的环化作为关键步骤。与氨基缩醛7相比，讨论了氨基缩醛4和8与Pictet-Spengler反应的不同过程。

  DOI：

  10.1016/s0040-4020(01)80944-3

文献信息

• Tetrahydro-.beta.-carboline derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04625032A1

  公开（公告）日：1986-11-25

  Tetrahydro-.beta.-carboline derivative of the formula: ##STR1## wherein R.sup.2 is lower alkyl, and either (A) R.sup.1 is hydroxymethyl or carboxy, R.sup.3 and R.sup.4 are both hydrogen, and X is halogen, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or (B) R.sup.1 is hydrogen, carboxy-lower alkyl or a group of the formula: --CH.sub.2 OY, Y is lower alkyl, lower alkanoyl or an oxygen-containing monocyclic heterocyclic group, R.sup.3 is hydrogen, hydroxy-lower alkyl or carboxy, R.sup.4 is hydrogen or hydroxy-lower alkyl, and X is hydrogen, or a salt thereof, which has excellent activities for alleviating, curing and preventing hepatic damages and is useful as a therapeutic or prophylactic agent for hepatic diseases.

  Tetrahydro-.beta.-carboline衍生物的化学式：##STR1##其中R.sup.2是较低的烷基，且要么（A）R.sup.1是羟甲基或羧基，R.sup.3和R.sup.4都是氢，X是卤素、较低的烷基、较低的烷氧基、羟基或苄氧基；或者（B）R.sup.1是氢、羧基较低的烷基或化学式：--CH.sub.2 OY的基团，Y是较低的烷基、较低的烷酰基或含氧的单环杂环基团，R.sup.3是氢、羟基较低的烷基或羧基，R.sup.4是氢或羟基较低的烷基，X是氢或其盐，具有出色的活性，可用于缓解、治愈和预防肝损伤，并可作为治疗或预防肝病的药物。
• A SYNTHESIS OF HARMALINE
  作者：Ian D. Spenser

  DOI：10.1139/v59-272

  日期：1959.11.1

  The synthesis of 1-methyl-3,4-dihydro-β-carboline (harmalan) and of two of its derivatives by dehydration of the corresponding 1-hydroxymethyl-1,2,3,4-tetrahydro-β-carbolines is described. Harmalan was also obtained by oxidative decarboxylation of 1-methyl-1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid.

  通过将相应的1-羟甲基-1,2,3,4-四氢-β-咔啉脱水合成1-甲基-3,4-二氢-β-咔啉（harmalan）及其两种衍生物。Harmalan也可以通过氧化脱羧1-甲基-1,2,3,4-四氢-β-咔啉-1-羧酸来获得。
• Substrate engineering: Effects of different N-protecting groups in the CAL-B-catalysed asymmetric O-acylation of 1-hydroxymethyl-tetrahydro-β-carbolines
  作者：Rita Megyesi、Enikő Forró、Ferenc Fülöp

  DOI：10.1016/j.tet.2018.04.012

  日期：2018.5

  In the frame of substrate engineering, the steric effect of different N-protecting groups on the enantioselectivity and reaction rate of CAL-B-catalysed (S)-selective O-acylation of N-protected 1-hydroxymethyl-tetrahydro-β-carbolines was investigated. Excellent enantioselectivities (E > 200) were observed when the acylation of N-Boc [(±)-1], N-Cbz [(±)-3], and N-Fmoc-protected [(±)-4] substrates was

  在底物工程的框架内，不同的N保护基对CAL-B催化的N保护的1-羟甲基-四氢-β-咔啉的（S）-选择性O-酰化的对映选择性和反应速率的空间效应是调查。 当N -Boc [（±）-1 ]，N -Cbz [（±）-3 ]和N -Fmoc保护的[（±）-4 ]底物被酰化时，观察到极好的对映选择性（E > 200）。使用CAL-B和乙酸酐在60°C的甲苯中进行。N的分辨率-乙酰基保护的底物（±）-2在30分钟后显示出优异的E（> 200），但随着反应的进行，由于N → O和O → N的酰基迁移，E在2天后开始下降。（±）-3和（±）-4的制备性拆分导致未反应的氨基醇（R）-3和（R）-4和酯（S）-7a和（S）-8a具有良好的对映体过量（≥88） ％）和高收率（≥44％）。
• Enzymatic Strategy for the Resolution of New 1-Hydroxymethyl Tetrahydro-<i>β</i> -carboline Derivatives in Batch and Continuous-Flow Systems
  作者：Rita Megyesi、Enikő Forró、Ferenc Fülöp

  DOI：10.1002/open.201500203

  日期：2016.6

  o‐1,2,3,4‐tetrahydro‐β‐carboline [(±)‐9] were prepared through enzymecatalyzed asymmetric acylation of their primary hydroxyl group. The preliminary experiments were performed in a continuous‐flow system, while the preparative‐scale resolutions were done as batch reactions. Excellent enantioselectivities (E>200) were obtained with Candida antarctica lipase B (CAL‐B) and acetic anhydride in toluene

  许多含有四氢-β-咔啉骨架的生物碱具有众所周知的治疗作用，从而引起人们对这些天然产物合成的兴趣增加。N -Boc保护的1-羟甲基-1,2,3,4-四氢-β-咔啉的对映体[（±）-7 ]，1-羟甲基-6-甲氧基-1,2,3,4-四氢β-咔啉[（±）-8 ]和1-羟甲基-6-氟-2-1,2,3,4-四氢-β-咔啉[（±）-9通过酶催化的伯羟基的不对称酰化反应制备了[α]。初步实验是在连续流系统中进行的，而制备规模的拆分是作为间歇反应进行的。在60°C的甲苯溶液中，南极假丝酵母脂肪酶B（CAL-B）和乙酸酐获得了优异的对映选择性（E > 200）。具有高对映体过量的值（获得回收的醇和所产生的酯EE ≥96％）。将O-酰化对映体[（S）‐10 –（S）‐12）]转化为相应的氨基醇[（S）‐7 –（S）‐ 9）]进行甲醇分解。微波辅助的Boc清除还进行并导致相应的化合物中（[R ）- 4 - （[R
• Synthesis of 1,2,3,4-tetrahydro-.BETA.-carboline derivatives as hepatoprotective agents. IV. Positional isomers of 1,2,3,4-tetrahydro-2-methylthiothiocarbonyl-.BETA.-carboline-3-carboxylic acid and its 1-alkylated derivatives.
  作者：YUTAKA SAIGA、IKUO IIJIMA、AKIHIKO ISHIDA、TOSHIKAZU MIYAGISHIMA、NORIO TAKAMURA、TOKURO OH-ISHI、MAMORU MATSUMOTO、Yuzo MATSUOKA

  DOI：10.1248/cpb.35.3705

  日期：——

  Two tetrahydro-β-carboline-1-and-4-carboxylic acids (1b, c) and the corresponding hydroxymethyl derivatives (2b, c), which are positional isomers of the 3-carboxylic acid (1a) and its 3-hydroxymethyl derivative (2a), were synthesized and tested for hepatoprotective activity against carbon tetrachloride (CCl4) -induced liver damage in mice. The hepatoprotective activity of these positional isomers decreased in the following order;1a> 1b> 1c> and 2a > 2b>2c. The effect of alkyl substitution at the 1 position of 1a and 2a was also examined with the cis and trans isomers (5a, b-14a, b). Compounds with small alkyl groups such as Me and Et showed potent activity. Lengthening of the alkyl group generally caused a decrease in activity. In a series of the stereoisomers of the 3-carboxylic acids (5a, b-9a, b), the cis isomers tend to be more active than the trans counterparts.

  合成了两种四氢-β-咔啉-1和-4-羧酸（1b，c）及相应的羟甲基衍生物（2b，c），它们是3-羧酸（1a）及其3-羟甲基衍生物（2a）的位置异构体，并测试了它们对四氯化碳（CCl4）诱导的小鼠肝损伤的保肝活性。这些位置异构体的保肝活性依次降低：1a>1b>1c>和2a>2b>2c。顺式和反式异构体（5a、b-14a、b）也检测了 1a 和 2a 1 位上烷基取代的影响。带有小烷基（如 Me 和 Et）的化合物显示出强大的活性。烷基加长一般会导致活性降低。在一系列 3-羧酸立体异构体（5a、b-9a、b）中，顺式异构体的活性往往高于反式异构体。