(+/-)-Nornantenine | 65732-35-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (+/-)-Nornantenine
• 英文别名: 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]benzodioxolo[5,6-g]quinoline；(+)-nornantenine；nornantenine；1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]dioxolo[4',5':4,5]benzo[1,2-g]quinoline；1,2-Dimethoxy-9,10-methylendioxy-noraporphin；dl-Nornantenine；18,19-dimethoxy-5,7-dioxa-13-azapentacyclo[10.7.1.02,10.04,8.016,20]icosa-1(20),2,4(8),9,16,18-hexaene
• CAS: 65732-35-6
• 化学式: C₁₉H₁₉NO₄
• 分子量: 325.364
• InChiKey: JWXKBCGJLCEZTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-Nornantenine 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 1,2-dimethoxy-6-ethyl-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]benzodioxolo[5,6-g]quinoline
  参考文献：
  名称：

  Structure–activity relationship studies with (±)-nantenine derivatives for α1-adrenoceptor antagonist activity

  摘要：

  A series of (+/-)-nantenine derivatives of the natural aporphine alkaloids was synthesized and examined for a blocking action on a, adrenoceptors in rat aorta and A10-cells. The potency of these derivatives was compared with that of an aporphine-related compounds (+)boldine, an alpha(1)-adrenoceptor antagonist. Among nine (+/-)-nantenine derivatives having different substituents at N-6, C-1, or C-4 of the aporphine skeleton, (+/-)-domesticine had the most powerful ot alpha(1) -adrenoceptor-blocking action. The order of pA(2) values was (+/-)-domesticine (8.06 +/- 0.06)>(+/-)-nordomesticine (7.34 +/- 0.03)>(+/-)-nantenine(7.03 +/- 0.03)>(+)-boldine(6.91 +/- 0.02)> other derivatives. Study of the structure -activity relationships showed that the replacement of a methoxy moiety at C-1 position of (+/-)-nantenine with a hydroxyl group increased affinity for the receptor. In contrast, replacement of a methyl group with a hydrogen atom or an ethyl group at N-6 position in the (+/-)-nantenine structure decreased affinity for the receptor. These results suggest that a hydroxyl group at the C-1 position and a methyl group at the N-6 position in the (+/-)-nantenine structure are essential for the enhancement of affinity for the alpha(1)-adrenoceptor. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0014-2999(02)01303-1
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 三氟乙酸 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 58.0h， 生成 (+/-)-Nornantenine
  参考文献：
  名称：

  阿朴菲类生物碱的制备方法

  摘要：

  本发明公开了一种如式III所示的阿朴菲类生物碱的制备方法，以式III‑0苯甲醛类化合物为原料，依次进行Wittig反应、Pictet‑Spengler反应、Heck反应、钯碳氢解脱保护。本发明选择原料含溴的苯甲醛类衍生物为原料，通过溴原子增加碳碳偶联产率和反应速率，提高反应活性；采用氯甲酸苄酯进行NH保护，引入吸电子基团有助于提高反应产率；采用一锅煮方法直接在酸催化体系中使苯乙烯甲基醚衍生物和酰化后的苯乙胺衍生物反应得到苄基四氢异喹啉。本发明制备方法反应条件温和，所用试剂低毒，原料易得，后处理方便，且反应路线较以往报道更简洁，可适用于多种反应底物。

  公开号：

  CN112920119B

文献信息

• Microwave-assisted direct biaryl coupling: first application to the synthesis of aporphines
  作者：Sandeep Chaudhary、Stevan Pecic、Onica LeGendre、Wayne W. Harding

  DOI：10.1016/j.tetlet.2009.03.029

  日期：2009.5

  microwaves in a direct biaryl coupling reaction for the synthesis of analogs of the aporphine alkaloid nantenine. Our study shows that the aporphine core may be rapidly accessed from benzyl-tetrahydroisoquinoline substrates with this method. This is the first report of a microwave-assisted direct biaryl coupling reaction in the synthesis of aporphine molecules.

  我们研究了微波在直接联芳基偶联反应中用于合成阿朴啡生物碱 nantenine 类似物的用途。我们的研究表明，使用这种方法可以从苄基四氢异喹啉底物快速获得阿朴啡核心。这是阿朴啡分子合成中微波辅助直接联芳基偶联反应的首次报道。
• (±)-Nantenine analogs as antagonists at human 5-HT2A receptors: C1 and flexible congeners
  作者：Sandeep Chaudhary、Stevan Pecic、Onica LeGendre、Hérnan A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmcl.2009.03.048

  日期：2009.5

  C1 and flexible analogs of (+/-)-nantenine were synthesized and evaluated for antagonist activity at human 5-HT(2)A receptors in a calcium mobilization assay. This work has resulted in the identification of the most potent 5-HT2A antagonist known based on an aporphine. Our results also suggest that the C1 position may be a key site for increasing 5-HT2A antagonist activity in this compound series. In addition, the structural rigidity of the aporphine core appears to be required for nantenine to function as a 5-HT2A antagonist. Published by Elsevier Ltd.
• Affinity of aporphines for the human 5-HT2A receptor: Insights from homology modeling and molecular docking studies
  作者：Stevan Pecic、Pooja Makkar、Sandeep Chaudhary、Boojala V. Reddy、Hernan A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmc.2010.06.043

  日期：2010.8

  Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K-e) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. Published by Elsevier Ltd.
• New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine
  作者：Sandeep Chaudhary、Shashikanth Ponnala、Onica LeGendre、Junior A. Gonzales、Hernán A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmc.2011.08.019

  日期：2011.10

  A series of Cl, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT2A and alpha(1A) receptor functional assays. Alkyl substitution of the Cl and N6 methyl groups of nantenine provided selective 5-HT2A and alpha 1A antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for alpha(1A) versus 5-HT2A. The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT2A antagonists known presently. (C) 2011 Elsevier Ltd. All rights reserved.
• Jossang, Akino; Leboeuf, Michel; Cave, Andre, Heterocycles, 1987, vol. 26, # 8, p. 2191 - 2198
  作者：Jossang, Akino、Leboeuf, Michel、Cave, Andre

  DOI：——

  日期：——