methyl 2,3,4-tri-O-isobutyryl-D-glucopyranuronate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2,3,4-tri-O-isobutyryl-D-glucopyranuronate
• 英文别名: methyl (2S,3S,4S,5R)-6-hydroxy-3,4,5-tris(2-methylpropanoyloxy)oxane-2-carboxylate
• 化学式: C₁₉H₃₀O₁₀
• 分子量: 418.441
• InChiKey: AUBWOCDKQXZRRC-PQZNDWDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 2,3,4-tri-O-isobutyryl-D-glucopyranuronate 在 4 A molecular sieve 、 三氟化硼乙醚 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 morphine-3,6-di(methyl 2,3,4-tri-O-isobutyryl-β-D-glucopyranuronate)
  参考文献：
  名称：

  A Simple Synthesis of Morphine-3,6-di-β-d-glucuronide

  摘要：

  A convenient two-step synthesis of morphine-3,6-di-beta-D-glucuronide in fair yield from morphine and methyl 2,3,4-tri-O-isobutyryl-1-O-trichloroacetimidoyl-alpha-D-glucopyranuronate is reported. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00664-5
• 作为产物：
  描述：

  甲基1,2,3,4-四-O-异丁酰基-beta-D-葡萄糖醛酸酯 在 一水合肼 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以94%的产率得到methyl 2,3,4-tri-O-isobutyryl-D-glucopyranuronate
  参考文献：
  名称：

  用于检测睾酮滥用的 3α,6β-Dihydroxyandrostan-17-one 3-Glucuronides 的合成

  摘要：

  一种方便且可扩展的合成提供了 3-葡糖苷酸结合物，这些结合物在兴奋剂控制研究中被确定为内源性雄激素合成代谢类固醇滥用的长期标志物。合成缀合物的 UHPLC-MS/MS 分析与从尿代谢物中获得的结果相匹配。该合成的特点是在类固醇骨架上立体选择性地引入 5α/5β 氢和 6β-羟基，以及温和的施密特三氯乙酰亚胺糖基化方法。

  DOI：

  10.1002/ejoc.202200177

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。
• Synthesis of stable isotope-labeled metabolites of asenapine
  作者：Jeffrey T. Kuethe

  DOI：10.1002/jlcr.2924

  日期：2012.5.15

  The stable isotope-labeled synthesis of four of the major metabolites of asenapine is described. The synthesis of [13CD3]-asenapine N-oxide proceeded in two synthetic steps. Preparation of [13CD3]-asenapine 11-hydroxysulfate and [13C6]-N-desmethylasenapine paralleled established synthetic protocols with effective utilization of labeled precursors. The synthesis of [13CD3]-asenapine N+-glucuronide was achieved in three chemical steps followed by purification.

  本文介绍了用稳定同位素标记合成四种阿塞那平主要代谢物的方法。13CD3]-asenapine N-氧化物的合成分为两个合成步骤。[13CD3]-阿塞那平 11-羟基硫酸盐和[13C6]-N-去甲基阿塞那平的制备与既定的合成方案一致，并有效地利用了标记的前体。13CD3]-asenapine N+-葡萄糖醛酸的合成分为三个化学步骤，然后进行纯化。
• 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）。
• A convenient new synthesis of quaternary ammonium glucuronides of drug molecules
  作者：Lisa Iddon、Ryan A. Bragg、John R. Harding、Andrew V. Stachulski

  DOI：10.1016/j.tet.2009.10.113

  日期：2010.1

  N-Glucuronides, of various Structural types, are frequently encountered as drug metabolites. Efficient chemical synthesis of these compounds, both as analytical standards and for toxicological investigation, is therefore an important goal. Earlier syntheses of N+-glucuronides of aliphatic tertiary amine drugs involved direct reaction of the drug molecule with a bromosugar, but yields were generally low and of poor reproducibility, with many by-products. In addition the final products were often of low stability, hindering effective isolation and purification. We now report that a stable, readily prepared glucuronic acid hemiacetal is a reliable precursor for metabolites of this type and give three pharmaceutically relevant examples. We report further on the stability of the final metabolites and the conditions required for their isolation and purification. (C) 2009 Elsevier Ltd. All rights reserved.