(1R,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid

• 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: (1R,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
• 英文别名: 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid；(1R,3R)-1-methyl-1,2,3,4-tetrahydropyridino[3,4-b]indol-3-formic acid；(+)-(1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid；(1R,3R)-1-methyl-2,3,4,9-tetrahydropyrido[3,4-b]Indole-3-carboxylic acid；1-Methyl-1,2,3,4-tetrahydrocarbolin-2-ium-3-carboxylate；(1R,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: ZUPHXNBLQCSEIA-RDDDGLTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 11.0h， 生成 (10R,15S)-10,13-dimethyl-12-sulfanylidene-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-14-one
  参考文献：
  名称：

  Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimer's disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki-Miyaura cross-coupling reaction of 11a-d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.028
• 作为产物：
  描述：

  乙醛 、 D-色氨酸 在 硫酸 作用下， 反应 6.0h， 生成 (1R,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimer's disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki-Miyaura cross-coupling reaction of 11a-d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.028

文献信息

• Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore
  作者：Lu Zhang、Wei Li、Taifeng Xiao、Zehua Song、René Csuk、Shengkun Li

  DOI：10.1021/acs.jafc.8b02778

  日期：2018.8.29

  toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates

  受成熟的琥珀酸脱氢酶抑制剂（SDHIs）的启发，我们对发现手性抗真菌酰胺的不懈努力转向使用2-（2-恶唑啉基）苯胺作为已知药效团优化其极性区域。脚手架跳跃和生物活性指导的收敛合成使有希望的抗真菌类别的鉴定。取代基和手性的精细调节提供了7种酰胺（1s，1t，2d，2h，2j，3k和2l）作为抗真菌候选物，其EC 50值低于5 mg / L。进行了无环酸手性酰胺作为SDHIs的首次研究，选择2d作为灰葡萄孢的有希望的候选物，其在50 mg / L时的预防效果高达93.9％，优于Boscalid。针对化合物2d及其非对映异构体，模拟了具有不同构型的化合物之间的不同结合模型。合成可及性和成本效益的优势突出了化合物2d作为已知SDHI杀菌剂的良好替代品的实际潜力。
• Microwave accelerated Pictet–Spengler reactions of tryptophan with ketones directed toward the preparation of 1,1-disubstituted indole alkaloids
  作者：Fu-Ming Kuo、Ming-Chung Tseng、Ya-Hew Yen、Yen-Ho Chu

  DOI：10.1016/j.tet.2004.10.025

  日期：2004.12

  Using the Pictet–Spengler reactions of tryptophan with aldehydes under acidic conditions at ambient temperature, diastereoisomers of 1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines could readily be furnished in short time (0.5–4 h) with good to excellent yields (50–98%). Though intrinsically slow in reaction rates, ketone reactions can be accelerated (from days to minutes) using microwaves in open

  使用色氨酸与醛在环境温度下的酸性条件下的Pictet-Spengler反应，可以轻松地在短时间内（0.5–4小时）提供1,3-二取代-1,2,3,4-四氢-β-咔啉的非对映异构体），具有良好至极佳的收率（50–98％）。尽管反应速度本质上很慢，但在开放的容器中使用微波可以加速酮的反应（从几天到几分钟），分离产率高（67-99％），这使这些咔啉成为合成天然和非天然吲哚生物碱的可行反应中间体。 。简要讨论了两种吲哚生物碱的制备，即四氢-β-咔啉二酮哌嗪和四氢-β-咔啉乙内酰脲。
• ß-CARBOLINE, DIHYDRO-ß-CARBOLINE AND TETRAHYDRO-ß-CARBOLINE ALKALOID DERIVATIVES AND PREPARATION METHODS SAME AND USE IN ASPECTS OF PREVENTING AND TREATING PLANT VIRUSES, FUNGICIDES AND INSECTICIDES
  申请人：NANKAI UNIVERSITY

  公开号：US20160326166A1

  公开（公告）日：2016-11-10

  The present invention relates to β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) and a method for preparing same and the use in the aspects of preventing and treating plant viruses, fungicides and insecticides. For the meaning of each group in formula (I) see the description. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives of the present invention show a particularly ourstanding anti-plant virus activity, and also have fungicidal and insecticidal activities.

  本发明涉及β-咔啉、二氢β-咔啉和四氢β-咔啉生物碱衍生物(I)，以及其制备方法和在预防和治疗植物病毒、杀菌剂和杀虫剂方面的用途。本发明中的β-咔啉、二氢β-咔啉和四氢β-咔啉生物碱衍生物显示出特别出色的抗植物病毒活性，同时还具有杀菌和杀虫活性。
• 一种β咔啉类化合物中间体的制备方法及其应用
  申请人：京博农化科技有限公司

  公开号：CN112142734B

  公开（公告）日：2022-05-31

  本发明提供了一种β咔啉类化合物中间体的制备方法及其应用，属于化工技术领域，所述制备方法包括如下步骤：将L‑色氨酸、乙醛、甲醇的水溶液、路易斯酸、布朗斯特酸和手性胺混合，将得到的混合物进行合成反应，得到β咔啉类化合物中间体(1S，3S)‑1‑甲基‑2，3，4，9‑四氢吡啶并[3，4‑b]吲哚‑3‑甲酸。本发明制备得到的(1S，3S)‑1‑甲基‑2，3，4，9‑四氢吡啶并[3，4‑b]吲哚‑3‑甲酸，不仅产品收率高，且ee值高。
• Design, synthesis, anti-TMV, fungicidal, and insecticidal activity evaluation of 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid derivatives based on virus inhibitors of plant sources
  作者：Hong-jian Song、Yong-xian Liu、Yu-xiu Liu、Yuan-qiong Huang、Yong-qiang Li、Qing-min Wang

  DOI：10.1016/j.bmcl.2014.09.063

  日期：2014.11

  arboxylic acid derivatives were designed and synthesized, and first evaluated for their anti-TMV, fungicidal and insecticidal activities. Most of these derivatives exhibited good antiviral activity against TMV both in vitro and in vivo. Especially, the activities of compounds 8 and 15 in vivo were higher than that of ribavirin. The compound 8 exhibited more than 70% fungicidal activities against Cercospora

  借鉴植物农药的创作思路，设计合成了一系列四氢-β-咔啉-3-羧酸衍生物，并对其抗TMV，杀真菌和杀虫活性进行了评价。这些衍生物中的大多数在体外和体内均表现出对TMV的良好抗病毒活性。特别是，化合物8和15的体内活性高于利巴韦林。化合物8显示出超过70种％的杀菌活性对尾孢堀花生，茄链格孢，蠕玉米小斑病，和稻纹枯病菌在50毫克/公斤，化合物16和20表现出对Mythimna sepepa和Ostrinia nubilalis的60％以上的杀虫活性。