3',4'-dimethyl-N-(trifluoroacetyl)norbelladine | 65303-63-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 3',4'-dimethyl-N-(trifluoroacetyl)norbelladine
• 英文别名: 4-[2-[(3,4-Dimethoxybenzyl)(trifluoroacetyl)amino]ethyl]phenol；N-[(3,4-dimethoxyphenyl)methyl]-2,2,2-trifluoro-N-[2-(4-hydroxyphenyl)ethyl]acetamide
• CAS: 65303-63-1
• 化学式: C₁₉H₂₀F₃NO₄
• 分子量: 383.367
• InChiKey: CVCQFCUFDRRQQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3',4'-dimethyl-N-(trifluoroacetyl)norbelladine 在 咪唑 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 2,2,2-三氟乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 11-(tert-butyldiphenylsiloxy)-6-(trifluoroacetyl)-2,3-dimethoxy-5,6,7,8-tetrahydrodibenz[c,e]azocine
  参考文献：
  名称：

  An Oxidative Intramolecular Phenolic Coupling Reaction for the Synthesis of Amaryllidaceae Alkaloids Using a Hypervalent Iodine(III) Reagent

  摘要：

  The oxidative intramolecular phenolic coupling reaction of norbelladine derivatives (1) was investigated with the aim of preparing amaryllidaceae alkaloids. Spirodienone compounds (2), which are intermediates for the synthesis of an amaryllidaceae alkaloid, (+)-maritidine, or phenol ether derivatives containing the 5,6,7,8-tetrahydrobenzazocine systems (9), were selectively obtained by the reaction of 1 and the hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA). Both p-p' coupling (11) and p-o' coupling spirodienone compounds (12) were obtained by the reaction of phenol derivatives having an alkoxy group at the C-3' position (10) with PIFA.

  DOI：

  10.1021/jo9606766
• 作为产物：
  描述：

  3,4-二甲氧基苄醇 在 polymer bound aminomethyl pyridine 、 polymer supported borohydride reagent 、 polymer supported perruthenate reagent 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 3',4'-dimethyl-N-(trifluoroacetyl)norbelladine
  参考文献：
  名称：

  Synthesis of the alkaloids (±)-oxomaritidine and (±)-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents

  摘要：

  本文介绍了高产率合成生物碱 (±)-oxomaritidine 1 和 (±)-epimaritidine 2 的简明方法，分别采用了五步和六步反应序列，仅使用聚合物支持的试剂，以协调的连续方式进行。

  DOI：

  10.1039/a901798d

文献信息

• 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells
  作者：Sean Henry、Ria Kidner、Mary R. Reisenauer、Igor V. Magedov、Robert Kiss、Véronique Mathieu、Florence Lefranc、Ramesh Dasari、Antonio Evidente、Xiaojie Yu、Xiuye Ma、Alexander Pertsemlidis、Regina Cencic、Jerry Pelletier、David A. Cavazos、Andrew J. Brenner、Alexander V. Aksenov、Snezna Rogelj、Alexander Kornienko、Liliya V. Frolova

  DOI：10.1016/j.ejmech.2016.05.004

  日期：2016.9

  alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy

  石蒜科的植物产生各种各样的生物碱和非碱性次生代谢产物，其中许多因其有希望的抗癌活性而被研究。其中，最近显示基于5,10b-乙基菲啶环系统的可丽宁型生物碱可有效抑制对各种促凋亡刺激具有抵抗力的癌细胞的增殖，并代表对当前化疗难以耐受的肿瘤，例如神经胶质瘤，黑色素瘤，非小细胞肺癌，食道癌，头颈癌等。以这一发现为出发点，并利用简洁的仿生路线通往可丽宁骨架，合成了一系列可丽宁类似物，并针对癌细胞进行了评估。这些化合物表现出一位数的微摩尔活性，并在多种耐药性癌细胞培养物中保留了这种活性。这项研究导致发现了新的双环系统，在开发能够克服癌症化疗耐药性的有效临床抗癌药物中具有巨大潜力。
• A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly
  作者：Ian R. Baxendale、Jon Deeley、Charlotte M. Griffiths-Jones、Steven V. Ley、Steen Saaby、Geoffrey K. Tranmer

  DOI：10.1039/b600382f

  日期：——

  A flow process for the multi-step synthesis of the alkaloid natural product (±)-oxomaritidine is described, mediated through the use of microfluidic pumping systems that progress material through various packed columns containing immobilized reagents, catalysts, scavengers or catch and release agents; our route involves the combination of seven separate synthetic steps linked into one continuous sequence utilizing flow chemistry.

  本文介绍了一种多步骤合成生物碱天然产物 (±)-oxomaritidine 的流动工艺，该工艺通过使用微流体泵系统，使材料通过含有固定试剂、催化剂、清除剂或捕获和释放剂的各种填料柱。
• A Novel and Useful Oxidative Intramolecular Coupling Reaction of Phenol Ether Derivatives on Treatment with a Combination of Hypervalent Iodine(III) Reagent and Heteropoly Acid
  作者：Hiromi Hamamoto、Gopinathan Anilkumar、Hirofumi Tohma、Yasuyuki Kita

  DOI：10.1002/1521-3765(20021202)8:23<5377::aid-chem5377>3.0.co;2-h

  日期：2002.12.2

  The oxidative intramolecular coupling reaction of phenol ether derivatives (nonphenolic derivatives) on treatment with a novel combination of a hypervalent iodine(III) reagent, phenyliodine bis(trifluoroacetate) (PIFA), and heteropoly acid (HPA) was studied. Biaryl compounds were obtained in excellent yields on treatment of highly substituted phenol ethers. On the other hand, spirodienones were specifically

  研究了酚醚衍生物（非酚类衍生物）在高价碘试剂，苯基碘双三氟乙酸酯（PIFA）和杂多酸（HPA）的新型组合下的氧化分子内偶联反应。通过处理高度取代的酚醚，可以以极好的收率获得联芳基化合物。另一方面，当优选的芳基偶联位点之一在对位被甲氧基取代时，特异形成螺二烯酮。
• A General Electro‐Synthesis Approach to Amaryllidaceae Alkaloids
  作者：Dennis Pollok、Luca M. Großmann、Torsten Behrendt、Till Opatz、Siegfried R. Waldvogel

  DOI：10.1002/chem.202201523

  日期：2022.9.6

  Highly pharmaceutically relevant Amaryllidaceae alkaloids have been accessed by a versatile electro-organic key transformation, including a precursor of the acetylcholinesterase inhibitor galantamine, used as FDA-approved drug for the treatment of Alzheimer's disease. Spirodienone-type intermediates were obtained in a regioselective and sustainable anodic key transformation from nature-derived starting

  高度药学相关的石蒜科生物碱已通过多功能电有机关键转化获得，其中包括乙酰胆碱酯酶抑制剂加兰他敏的前体，该药物被 FDA 批准用作治疗阿尔茨海默病的药物。螺二烯酮型中间体是通过区域选择性和可持续的阳极关键转化从天然原料中获得的
• Methods for treatment of resistant cancer
  申请人：New Mexico Tech University Research Park Corporation

  公开号：US10414778B2

  公开（公告）日：2019-09-17

  The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.

  本公开内容描述了一种利用可靶向抗药性癌细胞的化合物治疗包括癌症在内的各种疾病的方法。本发明的化合物可以降低抗药性癌细胞的增殖速度，如胶质瘤、肺癌和子宫肉瘤。