methyl O¹,O²,O³,O⁴-tetra(2,2-dimethyl-1-oxopropyl)-β-D-glucuronate | 86448-91-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl O¹,O²,O³,O⁴-tetra(2,2-dimethyl-1-oxopropyl)-β-D-glucuronate
• 英文别名: methyl tetra-O-pivaloyl-β-D-glucopyranuronate；methyl 1,2,3,4-tetra-O-pivaloyl-β-D-glucopyranuronate；methyl (2S,3S,4S,5R,6S)-3,4,5,6-tetrakis(2,2-dimethylpropanoyloxy)oxane-2-carboxylate
• CAS: 86448-91-1
• 化学式: C₂₇H₄₄O₁₁
• 分子量: 544.64
• InChiKey: UVVZYXYYDVUAQO-CWLGOENISA-N

物化性质

• 沸点：
  531.4±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl O¹,O²,O³,O⁴-tetra(2,2-dimethyl-1-oxopropyl)-β-D-glucuronate 在 碘代三甲硅烷 、 3 A molecular sieve 、 碘 、 四乙基氢氧化铵 、 copper(l) chloride 作用下， 以 1,2-二氯乙烷 、 异丙醇 、 乙腈 为溶剂， 反应 191.75h， 生成 雄酮葡萄糖醛酸
  参考文献：
  名称：

  Glucuronidation of steroidal alcohols using iodosugar and imidate donors

  摘要：

  我们报道了一项关于多种重要类固醇次级醇的葡萄糖醛酸化研究。研究对象包括雄酮7、表雄酮8、17-乙酰氧基雄甾烷-3α,17β-二醇9、11α-羟基孕酮10和3-苯甲酸雌二醇11。这些化合物首先采用Schmidt三氯乙酰亚胺酯方法进行葡萄糖醛酸化，并在此基础上对酰基取代基（即衍生物2和3）、路易斯酸催化剂以及加成顺序进行了调整优化。随后对照性实验采用我们近期描述的糖基碘供体4进行催化，分别利用N-碘代丁二酰亚胺（NIS）或多种金属盐作为催化剂。

  DOI：

  10.1039/b412217h
• 作为产物：
  描述：

  D-glucurono-6,3-lactone 以 吡啶 、 甲醇 、 氯仿 为溶剂， 反应 145.0h， 生成 methyl O¹,O²,O³,O⁴-tetra(2,2-dimethyl-1-oxopropyl)-β-D-glucuronate
  参考文献：
  名称：

  Vlahov, Jontscho; Snatzke, Guenther, Liebigs Annalen der Chemie, 1983, # 4, p. 570 - 574

  摘要：

  DOI：

文献信息

• Preparation, X-ray structure and reactivity of a stable glycosyl iodide
  作者：Jamie Bickley、Jennifer A. Cottrell、John R. Ferguson、Robert A. Field、John R. Harding、David L. Hughes、K. P. Ravindanathan Kartha、Jayne L. Law、Feodor Scheinmann、Andrew V. Stachulski

  DOI：10.1039/b302629a

  日期：——

  Highly selective reaction of methyl tetra-O-pivaloyl-β-D-glucopyranuronate 2 with iodotrimethylsilane or (Me3Si)2 and I2 affords, in excellent yield, the ‘disarmed’ glycosyl iodide 1 which has good stability at 20 °C and excellent stability at 0 °C; the X-ray crystal structure of 1 is described, along with a comparison of its utility as a glycosyl donor to that of the corresponding bromide.

  甲基四-O-叔丁酰基-β-D-吡喃葡萄糖苷酸2与碘三甲基硅烷或(Me3Si)2和I2发生高选择性反应，以优异的产率生成“解除武装”的糖基碘化物1，其在20°C下具有良好的稳定性，0°C下稳定性极佳；描述了1的X射线晶体结构，并将其作为糖基供体的效用与相应溴化物的效用进行了比较。
• 6-O-Glycosylation of Morphine Derivatives Using Thioglycosides as Glycosyl Donors
  作者：Igor Rukhman、Lev Yudovich、Gennadiy Nisnevich、Arie L. Gutman

  DOI：10.1055/s-2000-6413

  日期：——

  A novel approach was developed for the synthesis of the pharmaceutically important morphine and dihydromorphine 6-β-d-glucuronides. The key step involves a selective 6-O-glycosylation of 3-O-protected morphines and dihydromorphines with thioglycosides that serve as glycosyl donors in the presence of thiophilic promoters. This novel approach may be useful for the O-glycosylation of other alkaloid derivatives.

  针对合成在医药领域重要的吗啡和二氢吗啡-6-β-d-葡萄糖醛酸苷，开发了一种新颖的方法。关键步骤包括在硫亲和助推剂存在下，利用硫代糖苷作为糖基供体，对3-O-保护的吗啡和二氢吗啡进行选择性的6-O-糖基化反应。这一新颖方法可能对其他生物碱衍生物的O-糖基化具有应用价值。
• Glycosidation with a Disarmed Glycosyl Iodide:  Promotion and Scope
  作者：Jennifer A. Perrie、John R. Harding、Clare King、Deborah Sinnott、Andrew V. Stachulski

  DOI：10.1021/ol035475k

  日期：2003.11.1

  [reaction: see text] Glucuronyl iodide 1 has been studied in detail as a "disarmed" glycosyl donor. In a model reaction, using N-iodosuccinimide (NIS) as a promoter and 2-phenylethanol as acceptor, best results were obtained using NIS with I(2), followed by trimethylsilyltrifluoromethanesulfonate (TMSOTf). When a series of primary and secondary alcohols was glycosylated using these conditions, yields

  [反应：见正文]葡糖醛酸碘化物1作为“解除武装”的糖基供体已被详细研究。在模型反应中，使用N-碘代琥珀酰亚胺（NIS）作为促进剂，使用2-苯基乙醇作为受体，使用具有I（2），然后是三甲基甲硅烷基三氟甲磺酸盐（TMSOTf）的NIS可获得最佳结果。当使用这些条件将一系列伯醇和仲醇糖基化时，可获得60-83％的β-葡糖醛酸内酯。各种“非重”金属盐也有效地催化了模型反应，但导致了反应性较低的仲醇产生大量的α-产物。
• 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。
• Process for making morphine-6-glucuronide and its analogues using haloglucuronate ester intermediates
  申请人：UFC Limited

  公开号：US06642366B1

  公开（公告）日：2003-11-04

  A process for manufacturing morphine-6-glucuronide and related compounds of the general structure of Formula 1: wherein optionally substituted morphine is conjugated with an optionally substituted member of a new class of intermediates, namely, 1-haloglucuronate esters, in the presence of iodine or an iodinium compound. The conjugation may be followed by conversion of R1 of Formula 1 into hydrogen and/or the removal of the ester groups from the glucuronic residue at R2 of Formula 1.

  一种制造吗啡-6-葡萄糖醛酸盐及相关化合物的过程，其一般结构式为公式1：其中可选取代的吗啡与可选取代的新类中间体之一即1-卤代葡萄糖醛酸酯在碘或碘离子化合物的存在下结合。共轭作用后，可以将公式1中的R1转化为氢和/或从公式1中的R2的葡萄糖酸残基中去除酯基。