lycoraminone | 21041-10-1

• 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: lycoraminone
• 英文别名: Lycoraminon；(1R,12S)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9-trien-14-one
• CAS: 21041-10-1
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: UFQNQEIAGBZCBL-YOEHRIQHSA-N

物化性质

• 溶解度：
  氯仿：可溶；二甲基亚砜：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  -20°C

制备方法与用途

Dihydronarwedine 是Galanthamine（G188500）的代谢物，而Galanthamine是一种选择性乙酰胆碱酯酶抑制剂，并被用作治疗和预防阿尔茨海默病及其由神经元代谢减少引起的相关疾病的药物。

反应信息

• 作为反应物：
  描述：

  lycoraminone 在 lithium diisopropyl amide 、 二苯二硫醚 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以45%的产率得到加兰他敏
  参考文献：
  名称：

  通过区域选择性芳烃的插入，由GABA完全合成（±）-加兰他敏

  摘要：

  通过在GABA（γ-氨基丁酸）衍生物中进行关键的区域选择性芳烃插入反应，可在约5％的总收率下实现（±）-加兰他敏的总合成。提出的策略仅涉及两个亚临界温度反应和少于五个色谱纯化即可实现加兰他敏的合成。

  DOI：

  10.1039/c8ob03123a
• 作为产物：
  描述：

  加兰他敏 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 lycoraminone
  参考文献：
  名称：

  （±）-lycoramine的总合成。第一部分

  摘要：

  通过逐步构建环A和B，然后形成环C，最后建立环D，可以实现逐步合成（±）-lycoramine（一种金缕梅科生物碱）。由5-乙氧基-2-羟基苯甲醛（III）分五个步骤制得的γ-氰基-γ-（3-乙氧基-2-甲氧基苯基）二甲基二甲酸酯（VIII）的Dieckmann环化反应得到甲基5-氰基-5-（将3-乙氧基-2-甲氧基苯基）-2-氧代环己烷甲酸酯（IX）转化为4-乙酰氧基-7'-乙氧基-1'，2'-二氢-8'-甲氧基螺[环己烷-1,1'-萘] -4′（3′高）（XXII）通过一系列反应进行，包括Wittig和Friedel-Crafts。在该化合物上进行的施密特反应产生两个异构的内酰胺（VⅤ）和（XXⅥ），后者经N-甲基化，脱乙酰基化并氧化，得到7-乙氧基-2,3,4,5-四氢-6-甲氧基-2-甲基-1 H-螺环[2-苯并ze庚因-5,1'-环乙已烷] -1,4'-二酮（XXX）也可以来自天

  DOI：

  10.1039/j39680002947

文献信息

• Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment
  申请人：Galantos Pharma GmbH

  公开号：EP1777222A1

  公开（公告）日：2007-04-25

  The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline of neuronal cholinergic receptors and/or acting as chvlinesterase inhibitors and/or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. galanthamine, narwedine and lyeoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as "prodrugs", in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. The compounds of this invention may be used as medicaments for the treatment of human brain diseases associated with a cholinergic deficit, including the neurodegenerative diseases Alzheimer's and Parkinson's disease and the psychiatric diseases vascular dementia, schizophrenia and epilepsy.

  本发明涉及化合物，除了增强神经胆碱能受体对乙酰胆碱和胆碱的敏感性，或者作为胆碱酯酶抑制剂和/或神经保护剂之外，与其原始化合物相比具有增强的血脑屏障渗透性。这些化合物来源于属于石蒜科生物碱类的天然化合物，例如迎春碱、纳尔韦丁和莱奥拉明，或者来源于这些化合物的代谢物（无论是从化学结构上还是直接通过化学合成）。本发明的化合物可以直接与其靶分子相互作用，或者它们可以作为“前药”，意味着在到达体内的靶区域后，它们通过水解或酶攻击转化为原始的母体化合物，并且与其靶分子相互作用，或者两者兼而有之。本发明的化合物可用作治疗与胆碱缺乏相关的人类脑疾病的药物，包括神经退行性疾病阿尔茨海默病和帕金森病，以及精神疾病血管性痴呆、精神分裂症和癫痫。
• Syntheses and Preparations of Narwedine and Related Novel Compounds
  申请人：Tojo Suarez Gabriel

  公开号：US20080306257A1

  公开（公告）日：2008-12-11

  The present invention relates to a process for preparing racemic narwedine (which can be can be kinetically resolved) to yield (−)-narwedine and which is the biogenic precursor of (−)-galanthamine) and the use thereof as a starting material for producing (−)-galanthamine. The invention further includes processes for preparing (−)-galanthamine and (−)-galanthamine hydrobromide, as well as related novel compounds.

  本发明涉及一种制备外消旋纳尔韦丁的方法（可以进行动力学拆分），以产生（-）-纳尔韦丁，它是（-）-迷迭香碱的生物前体，并且作为生产（-）-迷迭香碱的起始物料的用途。该发明还包括制备（-）-迷迭香碱和（-）-迷迭香碱溴化物的方法，以及相关的新化合物。
• CHOLINERGIC ENHANCERS WITH IMPROVED BLOOD-BRAIN BARRIER PERMEABILITY FOR THE TREATMENT OF DISEASES ACCOMPANIED BY COGNITIVE IMPAIRMENT
  申请人：Maelicke Alfred

  公开号：US20070213318A1

  公开（公告）日：2007-09-13

  The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline of neuronal cholinergic receptors and/or acting as cholinesterase inhibitors and/or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. galanthamine, narwedine and lycoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as “pro-drugs”, in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. The compounds of this invention may be used as medicaments for the treatment of human brain diseases associated with a cholinergic deficit, including the neurodegenerative diseases Alzheimer's and Parkinson's disease and the psychiatric diseases vascular dementia, schizophrenia and epilepsy.

  本发明涉及化合物，除了增强神经元胆碱能受体对乙酰胆碱和胆碱的敏感性，或者作为胆碱酯酶抑制剂和/或神经保护剂外，与其母化合物相比，具有增强的血脑屏障渗透性。这些化合物是从天仙子科生物碱类天仙子碱，如无心菜碱、纳尔韦丁和百合碱，或其代谢物中派生的（通过其化学结构或直接通过化学合成）。本发明的化合物可以直接与其目标分子相互作用，也可以作为“前药”，在到达体内目标区域后，通过水解或酶攻击转化为原始母化合物，并像母化合物一样与其目标分子反应，或两者兼而有之。本发明的化合物可用作治疗与胆碱能缺陷相关的人类脑疾病的药物，包括神经退行性疾病阿尔茨海默病和帕金森病以及精神疾病血管性痴呆、精神分裂症和癫痫。
• Cholinergic Enhancers with Improved Blood-Brain Barrier permeability for the Treatment of Diseases Accompanied by Cognitive Impairment
  申请人：Maelicke Alfred

  公开号：US20080261954A1

  公开（公告）日：2008-10-23

  The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline, and their exogenous agonists, of neuronal cholinergic receptors and/or acting as cholinesterase inhibitors and/or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. Galanthamine, narwedine and lycoramine, or from metabolites of said compounds.

  本发明涉及一种化合物，除了增强神经元胆碱能受体及外源性激动剂对乙酰胆碱和胆碱的敏感性，以及作为胆碱酯酶抑制剂和/或神经保护剂外，还具有比其母体化合物更强的血脑屏障通透性。这些化合物是从天仙子科生物碱（例如迎春花碱，纳威丁和莲花碱）或其代谢物中衍生出来的（可以通过其化学结构或直接通过化学合成来实现）。
• Asymmetric Total Syntheses of (−)-Lycoramine, (−)-Lycoraminone, (−)-Narwedine, and (−)-Galanthamine
  作者：Satyajit Majumder、Abhinay Yadav、Souvik Pal、Arindam Khatua、Alakesh Bisai

  DOI：10.1021/acs.joc.2c00420

  日期：2022.6.17

  A concise asymmetric total synthesis of naturally occurring Amaryllidaceae alkaloids sharing dihydrobenzofuran scaffolds, (−)-galanthamine (1a), (−)-lycoramine (1b), (−)-narwedine (2a), and (−)-lycoraminone (2b), is reported. Orthoester Johnson–Claisen rearrangement of allyl alcohol (+)-9 (98% ee) in diisopropylethylamine furnished enantioenriched cyclohexene (+)-8 (97.4% ee) with a quaternary stereogenic

  一种简明的不对称全合成天然石蒜科生物碱共享二氢苯并呋喃支架、(-)-加兰他敏 ( 1a )、(-)-lycoramine ( 1b )、(-)-narwedine ( 2a ) 和 (-)-lycoraminone ( 2b ) , 被报道。烯丙醇 (+)- 9 (98% ee) 在二异丙基乙胺中的 Orthoester Johnson-Claisen 重排提供对映体富集的环己烯 (+)- 8 (97.4% ee) 和季立体中心。