甲基(5xi)-2,3,4-三-O-异丁酰基-1-O-(2,2,2-三氯亚氨代乙酰)-alpha-D-来苏-吡喃己糖酸酯 | 150607-96-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 甲基(5xi)-2,3,4-三-O-异丁酰基-1-O-(2,2,2-三氯亚氨代乙酰)-alpha-D-来苏-吡喃己糖酸酯
• 英文名称: methyl 2,3,4-tri-O-isobutyryl-1-O-trichloroacetimidoyl-α-D-glucopyranuronate
• 英文别名: Methyl 2,3,4-Tri-O-isobutyryl-1-O-trichloroacetimidoyl-alpha-D-glucopyranuronate；methyl (2S,3S,4S,5R,6R)-3,4,5-tris(2-methylpropanoyloxy)-6-(2,2,2-trichloroethanimidoyl)oxyoxane-2-carboxylate
• CAS: 150607-96-8
• 化学式: C₂₁H₃₀Cl₃NO₁₀
• 分子量: 562.829
• InChiKey: CCIDTXJAPRZHSL-BXIXQQKLSA-N

物化性质

• 熔点：
  64-66°C
• 沸点：
  506.7±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少量）、二氯甲烷（少量）、乙酸乙酯（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  甲基(5xi)-2,3,4-三-O-异丁酰基-1-O-(2,2,2-三氯亚氨代乙酰)-alpha-D-来苏-吡喃己糖酸酯 在 sodium hydroxide 、 三氟化硼 作用下， 以 二氯甲烷 为溶剂， 生成 N-(4-aminobutyl)normorphine-6-β-D-glucuronide
  参考文献：
  名称：

  Synthesis of a morphine-6-glucuronide hapten, N-(4-aminobutyl)normorphine-6-glucuronide, and related haptens

  摘要：

  For use as a hapten in the radioimmunoassay of morphine-6-glucuronide 2 (M6G), N-(4-aminobutyl)normorphine-6-glucuronide 12 has been prepared, together with related haptens, using the imidate coupling method developed for synthesis of M6G; a rebuttal of recent critical comments on our synthesis of M6G is included.

  DOI：

  10.1016/0040-4039(95)01786-h
• 作为产物：
  描述：

  D-GLUCURONIDEMETHYLESTERD-葡糖苷酸甲酯 在 吡啶 、 一水合肼 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 甲基(5xi)-2,3,4-三-O-异丁酰基-1-O-(2,2,2-三氯亚氨代乙酰)-alpha-D-来苏-吡喃己糖酸酯
  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。
• Glucuronidation of steroidal alcohols using iodosugar and imidate donors
  作者：John R. Harding、Clare D. King、Jennifer A. Perrie、Deborah Sinnott、Andrew V. Stachulski

  DOI：10.1039/b412217h

  日期：——

  We report a study of the glucuronidation of a number of important steroidal secondary alcohols. The alcohols studied are androsterone 7, epiandrosterone 8, 17-acetoxy-androstane-3α,17β-diol 9, 11α-hydroxyprogesterone 10, and 3-benzoylestradiol 11. These were first glucuronidated using the Schmidt trichloroacetimidate method with variations in acyl substituent (viz. derivatives 2 and 3), Lewis acid catalyst and order of addition. The results are contrasted with those obtained using our recently described glycosyl iodide donor 4, catalysed either by N-iodosuccinimide (NIS) or various metal salts.

  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。
• Synthesis of unlabelled and stable-isotope-labelled glucuronide metabolites of dapagliflozin and synthesis of stable-isotope-labelled dapagliflozin
  作者：Kai Cao、John A. Brailsford、Ming Yao、Janet Caceres-Cortes、Robert Espina、Samuel J. Bonacorsi

  DOI：10.1002/jlcr.3484

  日期：2017.3

  Two regioisomeric glucuronide metabolites of dapagliflozin (BMS-512148) were synthesized and used to elucidate the structures of dapagliflozin metabolites observed in human urine samples. The structures of the synthetic metabolites were assigned by heteronuclear multiple-bond correlation, ROESY, and total correlation spectroscopy experiments. Analogues of these metabolites containing carbon-13 as a

  合成了达格列净 (BMS-512148) 的两种区域异构葡萄糖醛酸代谢物，并用于阐明在人类尿液样本中观察到的达格列净代谢物的结构。合成代谢物的结构通过异核多键相关、ROESY 和全相关光谱实验确定。还制备了这些含有碳 13 作为稳定标记的代谢物的类似物，用作分析从参与临床研究的患者身上获得的尿样的内标。
• Putative metabolites of fulvestrant, an estrogen receptor downregulator. Improved glucuronidation using trichloroacetimidates
  作者：John R. Ferguson、John R. Harding、David A. Killick、Keith W. Lumbard、Feodor Scheinmann、Andrew V. Stachulski

  DOI：10.1039/b105397n

  日期：2001.11.15

  Following regioselective protection of the estrogen receptor downregulator fulvestrant (ICI 182,780) 1 as its 17-acetate 2 or 3-benzoate 4, the 3-sulfate 5 and 3- and 17-glucuronide conjugates 8 and 12 were prepared. Satisfactory preparation of 12 required use of the tri-O-isobutyryl imidate derivative 10 in conjunction with an inverse-addition technique not previously employed in glucuronidation. The value of this method for simpler aglycones is discussed together with a study of variations in donor acyl substituent and catalyst. Another putative metabolite, the 17-ketone 19, was prepared by direct oxidation of 1.

  在对雌激素受体下调剂氟维司群（ICI 182,780）1 的 17-乙酸酯 2 或 3-苯甲酸酯 4 进行区域选择性保护后，制备出 3-硫酸盐 5 以及 3-和 17-葡萄糖醛酸轭合物 8 和 12。要制备出令人满意的 12，需要使用三-O-异丁酰亚胺酯衍生物 10 并结合一种以前未在葡萄糖醛酸化中使用过的反加成技术。我们讨论了这种方法对较简单苷元的价值，并研究了供体酰基取代基和催化剂的变化。另一种可能的代谢物 17 酮 19 是通过直接氧化 1 制备的。
• Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers
  作者：Somraj Guha、Soundararasu Senthilkumar、Edgar Voß、Lutz F. Tietze

  DOI：10.1002/chem.202004154

  日期：2020.12

  diacetate 11 in the presence of TMSOTf gave the 18‐α‐glucuronide 9 a. The 18‐β‐glucuronide 15 b and the 20‐β‐glucuronide 16 b could be obtained by reaction of methyl 2,3,4‐tri‐O‐isobutyryl‐1α‐glucuronate trichloroacetimidate 14 and aldosterone 21‐acetate 8 in the presence of TMSOTf or BF3⋅OEt2. Finally, reaction of aldosterone 21‐acetate 8 and methyl 2,3,4‐triacetyl‐1α‐glucuronate trichloroacetimidate

  醛固酮1是盐皮质激素，它对血压有很大的影响，其葡糖醛酸苷是检测多种疾病的重要标志。在这里，我们描述了不同醛固酮18和20葡糖醛酸内酯的化学合成。在TMSOTf存在下，三甲基甲硅烷基2,3,4-三乙酰基-1-β-葡萄糖醛酸甲酯5b与醛固酮二乙酸酯11的反应得到18-α-葡萄糖醛酸9a。18-β葡萄糖醛酸苷15b中与20-β葡萄糖醛酸苷16b中可以通过甲基的反应而获得2,3,4-三ö异丁酰基1α葡糖醛三氯14和醛固酮21-乙酸酯8在将TMSOTf或BF的存在3 ⋅OEt 2。最后，在TMSOTf存在下，醛固酮21-乙酸8与2,3,4-三乙酰基-1α-葡萄糖醛酸三氯乙酰胺酸甲酯19反应，得到相应的18-β-三乙酰基葡萄糖醛酸甲酯9 b，然后将其转化为所需的醛固酮18 -β-葡萄糖醛酸3通过两个酶促转化。