(2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol | 119557-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol
• 英文别名: α-homonojirimycin；2,6-Dideoxy-2,6-imino-D-glycero-L-gulo-heptitol
• CAS: 119557-99-2
• 化学式: C₇H₁₅NO₅
• 分子量: 193.2
• InChiKey: CLVUFWXGNIFGNC-OVHBTUCOSA-N

物化性质

• 熔点：
  207 °C
• 沸点：
  432.0±45.0 °C(Predicted)
• 密度：
  1.479±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.61
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  113.18
• 氢给体数：
  6.0
• 氢受体数：
  6.0

制备方法与用途

制备方法

α-高野尻霉素(1) 是一个氮杂糖，单糖环结构中的一个氧原子被氨基取代；它显示出对体内糖链处理的显著影响力。α-高野尻霉素(1) 也是一个优良的糖苷酶抑制剂。它的抑制作用原理可以解释为谷氨酸或天冬酰胺的糖苷酶与氮杂糖的一个氨基结合形成离子键（1）。此外，α-高野尻霉素(1) 也可以用作治疗法布瑞氏症的有效药物先导化合物（该病由活性酶缺乏症 α-半乳糖苷酶A 引起）（2）。

反应信息

• 作为反应物：
  描述：

  正溴丁烷 、 (2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以38 mg的产率得到N-butyl-α-homonojirimycin
  参考文献：
  名称：

  α-Glucosidase-inhibitory iminosugars from the leaves of Suregada glomerulata

  摘要：

  A water extract of the leaves of Suregada glomerulata (Euphorbiaceae) was found to inhibit rat small intestinal alpha-glucosidase. An examination of the extract afforded 20 iminosugars including one pyrrolidine and 19 piperidines. The structures of the 10 new compounds (11-20) were determined by NMR, and MS spectroscopic data analyses, and chemical correlations. The novelty of the identified compounds mainly stems from the loss of a hydroxy at C-4 and the presence of an 8-hydroxyoctyl side chain. Nine N-alkyl derivatives including N-methyl (1a, 8a, and 13a), N-butyl (1b, 2b, and 9b) and N,N-dimethyl (1c, 2c, and 9c) were synthesized. The compounds were tested for rat small intestinal a-glucosidase inhibitory activity. In total, 15 compounds, including compounds 11, 12, 15, and 19 and the three derivatives 8a, 9b, and 13a, showed inhibitory activity with IC50 values less than 40 mu M. In vivo results showed that total alkaloids of S. glomerulata (10 mg/kg) and four major iminosugars 1, 2, 3, and 9 (10 mg/kg) can lower the postprandial blood glucose level after sucrose and starch load in healthy male ICR mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.048
• 作为产物：
  描述：

  (3aS,4R,6R,7R,7aS)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-7-methoxymethoxy-6-methoxymethoxymethyl-2,2-dimethyl-hexahydro-[1,3]dioxolo[4,5-c]pyridine 在 盐酸 作用下， 以 甲醇 为溶剂， 以68%的产率得到(2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol
  参考文献：
  名称：

  （+）-α-曲霉霉素的全合成

  摘要：

  利用烯丙醇3作为非碳水化合物手性结构单元，在13个步骤中完成了（+）-α-homonojirimycin的合成，这是天然氮杂庚糖的第一个例子。

  DOI：

  10.1039/c39900001457

文献信息

• NOVEL COMPOSITIONS FOR PREVENTING AND/OR TREATING DEGENERATIVE DISORDERS OF THE CENTRAL NERVOUS SYSTEM
  申请人：Boyd Robert

  公开号：US20110092541A1

  公开（公告）日：2011-04-21

  The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.

  本发明提供了新颖的化合物，以及使用这些化合物预防和/或治疗中枢神经系统退行性疾病的组合物和方法。具体来说，本发明提供了预防和/或治疗帕金森病的方法。
• Imino and amino sugar purification
  申请人：Major Michael

  公开号：US20060293515A1

  公开（公告）日：2006-12-28

  Novel processes for the purification of an imino or amino sugar, such as D-1-deoxygalactonojirimycin (DGJ). Particularly, there are described processes for the purification of multi-kilogram scale sugars using hydrochloric acid.

  一种用于纯化亚胺或氨基糖的新型工艺，例如D-1-去氧半乳糖酮基脲胺（DGJ）。特别描述了使用盐酸纯化多公斤级糖的工艺。
• Method for the treatment of Pompe disease using 1-deoxynojirimycin and derivatives
  申请人：Mugrage Benjamin

  公开号：US20060264467A1

  公开（公告）日：2006-11-23

  The present invention provides a method for increasing the activity of a mutant or wild-type α-glucosidase enzyme in vitro and in vivo by contacting the enzyme with a specific pharmacological chaperone which is a derivative of 1-deoxynojirimycin. The invention also provides a method for the treatment of Pompe disease by administration of chaperone small molecule compound which is a derivative of 1-deoxynojirimycin. The 1-deoxynojirimycin derivative is substituted at the N or C1 position. Combination therapy with replacement α-glucosidase gene or enzyme is also provided.

  本发明提供了一种通过将酶与一种特定的药理伴侣接触来增加体外和体内突变型或野生型α葡萄糖苷酶酶活性的方法，该药理伴侣是1-去氧诺吉霉素的衍生物。该发明还提供了一种通过给予1-去氧诺吉霉素衍生物的伴侣小分子化合物来治疗庞贝病的方法。1-去氧诺吉霉素衍生物在N或C1位置被取代。还提供了与替代α葡萄糖苷酶基因或酶的联合治疗方法。
• [EN] GLYCOSIDASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE GLYCOSIDASES ET LEURS UTILISATIONS
  申请人：ALECTOS THERAPEUTICS INC

  公开号：WO2014032184A1

  公开（公告）日：2014-03-06

  The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

  该发明提供了用于抑制糖苷酶的化合物，这些化合物的前药，以及包括这些化合物或这些化合物的前药的药物组合物。该发明还提供了用于治疗与O-GlcNAcase缺乏或过度表达、O-GlcNAc的积累或缺乏相关的疾病和障碍的方法。
• An approach to 8 stereoisomers of homonojirimycin from d-glucose via kinetic &amp; thermodynamic azido-γ-lactones
  作者：Andreas F. G. Glawar、Sarah F. Jenkinson、Scott J. Newberry、Amber L. Thompson、Shinpei Nakagawa、Akihide Yoshihara、Kazuya Akimitsu、Ken Izumori、Terry D. Butters、Atsushi Kato、George W. J. Fleet

  DOI：10.1039/c3ob41334a

  日期：——

  Crystal structures were obtained for the two C2 epimeric azido-γ-lactones 2-azido-2-deoxy-3,5:6,7-di-O-isopropylidene-D-glycero-D-ido-heptono-1,4-lactone and 2-azido-2-deoxy-3,5:6,7-di-O-isopropylidene-D-glycero-D-gulo-heptono-1,4-lactone prepared from kinetic and thermodynamic azide displacements of a triflate derived from D-glucoheptonolactone. Azido-γ-lactones are very useful intermediates in the synthesis of iminosugars and polyhydroxylated amino acids. In this study two epimeric azido-heptitols allow biotechnological transformations via Izumoring techniques to 8 of the 16 possible homonojirimycin analogues, 5 of which were isolated pure because of the lack of stereoselectivity of the final reductive amination. A side-by-side glycosidase inhibition profile of 11 of the possible 16 HNJ stereoisomers derived from D-glucose and D-mannose is presented.

  获得两种 C2 差向叠氮-γ-内酯 2-叠氮-2-脱氧-3,5:6,7-二-O-异丙叉-D-甘油-D-ido-庚酮-1,4- 的晶体结构内酯和 2-叠氮基-2-脱氧-3,5:6,7-二-O-异亚丙基-D-甘油-D-古洛-庚酮-1,4-内酯由三氟甲磺酸酯的动力学和热力学叠氮化物置换制备来自D-葡萄糖庚酸内酯。叠氮基-γ-内酯是亚氨基糖和多羟基氨基酸合成中非常有用的中间体。在这项研究中，两种差向异构叠氮庚醇允许通过 Izumoring 技术对 16 种可能的高野尻霉素类似物中的 8 种进行生物技术转化，其中 5 种由于最终还原胺化缺乏立体选择性而被分离纯化。提出了衍生自 D-葡萄糖和 D-甘露糖的 16 种可能的 HNJ 立体异构体中的 11 种的并列糖苷酶抑制谱。