(6aS)-5,6,6a,7-四氢-1,9,10-三甲氧基-6-甲基-4H-二苯并[de,g]喹啉-2-醇 | 517-65-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 中文名称: (6aS)-5,6,6a,7-四氢-1,9,10-三甲氧基-6-甲基-4H-二苯并[de,g]喹啉-2-醇
• 英文名称: (+)-Predicentrine
• 英文别名: (S)-predicentrine；predicentrine；2-O-demethyl glaucine；Predicen-trine；Predicentrin；(6aS)-1,9,10-trimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-2-ol
• CAS: 517-65-7
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: OUTYMWDDJORZOH-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6aS)-5,6,6a,7-四氢-1,9,10-三甲氧基-6-甲基-4H-二苯并[de,g]喹啉-2-醇 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 三氟乙酸 为溶剂， 反应 2.0h， 以74%的产率得到3-bromopredicentrine
  参考文献：
  名称：

  Towards a more selective analogue of oxaliplatin: Synthesis of [Pt((1R,2R)-diaminocyclohexane)(3-carboxypredicentrinato)]

  摘要：

  A novel oxaliplatin analogue, [Pt((1R,2R)-diaminocyclohexane)(3-carboxypredicentrinato)], boldiplatin, has been synthesized by the coordination of the boldine derivative 3-carboxypredicentrinate to the corresponding platinum(II) moiety in 5.8% overall yield. The complex was fully characterized and biologically evaluated in vitro. Boldiplatin was compared with its parent drug oxaliplatin, showing equal activity over four human tumor cell lines (MCF-7, MDA-MB-231, PC-3 and HT-29) and a tenfold decrease in toxicity over a non-tumor cell line (DHF). This selectivity makes boldiplatin a good candidate for further evaluations to assess its potential as antitumor drug. (C) 2011 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.ica.2011.12.013
• 作为产物：
  描述：

  波尔定碱 在 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.17h， 生成 (6aS)-5,6,6a,7-四氢-1,9,10-三甲氧基-6-甲基-4H-二苯并[de,g]喹啉-2-醇
  参考文献：
  名称：

  Semisynthetic Studies on and Biological Evaluation of N-Methyllaurotetanine Analogues as Ligands for 5-HT Receptors

  摘要：

  N-Methyllaurotetanine (1) has been reported to display good affinity for the 5-HT1A receptor, but no structureaffinity studies have been performed to date. The commercially available alkaloid boldine (2) was used as the starting material for synthesis of various C-9 alkoxy analogues of N-methyllaurotetanine in order to gauge the effect of C-9 alkylation on affinity and selectivity at 5-HT1A, 5-HT2A, and 5-HT7 receptors. Mitsunobu reactions were implemented in the alkylation steps leading to the analogues. Modest improvement in 5-HT1A affinity was observed upon alkylation for most analogues. Thus, the C-9 hydroxy group of 1 is not critical for affinity to the 5-HT1A receptor. Some analogues displayed high affinity for the 5-HT7 receptor, comparable to N-methyllaurotetanine, with moderate selectivity vs 5-HT1A and 5-HT2A receptors.

  DOI：

  10.1021/np500893h

文献信息

• Antihyperglycemic Effect of Aporphines and their Derivatives in Normal and Diabetic Rats
  作者：Tzong-Cherng Chi、Shoei-Sheng Lee、Ming-Jai Su

  DOI：10.1055/s-2006-947199

  日期：2006.10

  The antihyperglycemic actions of some aporphines and their derivatives in normal Wistar, streptozotocin (STZ)-induced diabetic (IDDM) and nicotinamide-STZ induced diabetic (NIDDM) rats were investigated in this study. These compounds included thaliporphine, glaucine, boldine, N-methyllaurotetanine, and predicentrine and the derivatives, N-[2-(2-methoxyphenoxy)ethyl]norglaucine and diacetyl-N-allylsecoboldine. Bolus intravenous injection of these compounds decreased the plasma glucose levels in a dose-dependent manner in both normal and diabetic rats. Among them, thaliporphine was found to have the most potent antihyperglycemic effect in both NIDDM and IDDM diabetic rats. It was found that thaliporphine could stimulate the release of insulin in both normal and diabetic rats, and a dose of 1 mg per kg thaliporphine could significantly attenuate the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Similar treatment with thaliporphine significantly increased the skeletal muscle glycogen synthesis in both normal and diabetic rats. Hence, the hypoglycemic effect of thaliporphine in diabetic rats could be attributed to the stimulation of insulin release and the increase of glucose utilization.

  本研究调查了一些卟吩及其衍生物对正常 Wistar 大鼠、链脲佐菌素（STZ）诱导的糖尿病（IDDM）大鼠和烟酰胺-STZ 诱导的糖尿病（NIDDM）大鼠的降血糖作用。这些化合物包括他利吗啡、亮氨酸、波胆碱、N-甲基月桂四烯丙基酪氨酸、泼尼松肽和衍生物 N-[2-(2-甲氧基苯氧基)乙基]诺格亮氨酸和二乙酰基-N-烯丙基酪氨酸。静脉注射这些化合物可降低正常大鼠和糖尿病大鼠的血浆葡萄糖水平，其降低程度与剂量有关。结果发现，在 NIDDM 和 IDDM 糖尿病大鼠中，苯丙羟吗啡的降血糖作用最强。研究发现，无论是正常大鼠还是糖尿病大鼠，苯丙羟吗啡都能刺激胰岛素的释放，每公斤 1 毫克苯丙羟吗啡的剂量能显著降低正常大鼠静脉葡萄糖挑战试验引起的血浆葡萄糖升高。在正常大鼠和糖尿病大鼠中，使用相同剂量的苯丙羟吗啡都能明显增加骨骼肌糖原的合成。因此，他利吗啡对糖尿病大鼠的降血糖作用可归因于刺激胰岛素释放和提高葡萄糖利用率。
• Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from<i>Glaucium flavum</i>(Papaveraceae), in rat urine using GC-MS, LC-MSⁿand LC-high-resolution MSⁿ
  作者：Golo M.J. Meyer、Markus R. Meyer、Dirk K. Wissenbach、Hans H. Maurer

  DOI：10.1002/jms.3112

  日期：2013.1

  composition using HR‐MS. From these data, the following metabolic pathways could be proposed: O‐demethylation at position 2, 9 and 10, N‐demethylation, hydroxylation, N‐oxidation and combinations of them as well as glucuronidation and/or sulfation of the phenolic metabolites. For monitoring a glaucine intake in case of abuse or poisoning, the O‐ and N‐demethylated metabolites were the main targets for the

  甘氨酸（（S）-5,6,6a，7-四氢-1,2,9,10-四甲氧基-6-甲基-4H-二苯并[de，g]喹啉）是异喹啉生物碱，是黄精的主要成分。 （罂粟科）。据描述，它可以单独用作消遣性毒品，也可以与其他毒品合用。除此之外，在保加利亚和其他国家，青霉素还被用作止咳药。目前，尚无有关青光素代谢和毒理学分析的数据。为了研究两者，向Wistar大鼠口服给予了青光眼，并收集了尿液。对于代谢研究，尿液样品的处理包括蛋白质沉淀或酶促裂解，然后进行固相萃取。然后通过液相色谱（LC）结合低分辨率或高分辨率质谱（HR-MS）来测量样品。I和II期代谢物是通过对相应片段的详细解释来鉴定的，并通过使用HR-MS确定其元素组成来进一步证实。根据这些数据，可以提出以下代谢途径：2、9和10位的O-去甲基化，N-去甲基化，羟基化，N-氧化和它们的组合以及酚类代谢物的葡萄糖醛酸化和/或硫酸化。为了监测滥用或中毒情况下的青
• Manganese(III) acetate mediated oxidation of aporphines: a convenient and useful synthesis of oxoaporphines
  作者：Om V. Singh、Wei-Jan Huang、Chung-Hsiung Chen、Shoei-Sheng Lee

  DOI：10.1016/j.tetlet.2007.09.096

  日期：2007.11

  Manganese(III) acetate mediated oxidation of aporphines to oxoaporphines is described. The developed methodology was conveniently applied for the synthesis of naturally occurring oxoaporphine alkaloids, oxoglaucine, and atheroline, starting from commercially available boldine.

  描述了乙酸锰（III）介导的将磷灰石氧化为氧磷灰石。所开发的方法从商业上可买到的丁二烯开始，方便地用于合成天然存在的氧磷卟啉生物碱，氧磷月桂酸和动脉粥样碱。
• Structure–affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity
  作者：Marcelo Asencio、Claudio Hurtado-Guzmán、John J. López、Bruce K. Cassels、Philippe Protais、Abdeslam Chagraoui

  DOI：10.1016/j.bmc.2005.03.022

  日期：2005.6

  Halogenation of the aporphine alkaloid boldine at the 3-position leads to increased affinity for rat brain D-1-like dopaminergic receptors with some selectivity over D-2-like receptors. A series of 3-halogenated and 3,8-dihalogenated (halogen = Cl, Br or 1) derivatives of predicentrine (9-O-methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed for binding at D-1 and D-2 sites. Halogenation of predicentrine led to strong increases in affinity for D-1-like receptors, while the affinities for D-2-like receptors were either practically unchanged or reduced three- to fourfold. Halogenated glaucine derivatives did not show any clear trend towards enhanced selectivity, and the affinities were poor and similar to or worse than the values previously recorded for glaucine itself. Together with earlier work on boldine derivatives, these results suggest that the 2-hydroxy group on the aporphine skeleton may determine a binding mode favoring D-1-like over D-2-like receptors, with enhanced affinity when the C-3 position is halogenated. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and properties of glaucine-quinol
  作者：S. Philipov、O. Petrov、N. Mollov

  DOI：10.1016/s0040-4020(01)88694-4

  日期：1983.1