2,6-dideoxy-2,6-imino-D-glycero-L-galacto-heptitol

• 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: 2,6-dideoxy-2,6-imino-D-glycero-L-galacto-heptitol
• 英文别名: α-homogalactonojirimycin；α-homogalactostatin；(2R,3S,5S,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol
• 化学式: C₇H₁₅NO₅
• 分子量: 193.2
• InChiKey: CLVUFWXGNIFGNC-ZXXMMSQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  113
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-dideoxy-2,6-imino-D-glycero-L-galacto-heptitol 在 盐酸 作用下， 生成 (2R,3S,4S,5S,6R)-3,4,5-tris(hydroxy)-2,6-bis[(hydroxy)methyl]piperidinium hydrochloride
  参考文献：
  名称：

  Hong, Zhangyong; Liu, Lei; Sugiyama, Masakazu, Journal of the American Chemical Society, 2009, vol. 131, p. 8352 - 8353

  摘要：

  DOI：
• 作为产物：
  描述：

  6-Azido-7-O-tert-butyldimethylsilyl-6-deoxy-3,4-O-isopropylidene-1-O-methoxymethyl-α,β-D-gulo-hept-2-ulofuranose 在 palladium on activated charcoal 盐酸 、 四丁基氟化铵 、 水 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 生成 2,6-dideoxy-2,6-imino-D-glycero-L-galacto-heptitol
  参考文献：
  名称：

  The Synthesis of Deoxygalactostatin and 2,6-Imino-heptitol Derivatives via Stannane Mediated Hydroxymethylation of 5-Azido-1,4-lactones

  摘要：

  通过与 5-叠氮-1,4-内酯等效的羟甲基阴离子的亲核加成，可以获得脱氧半乳糖肽、同半乳糖霉素衍生物和其他 2,6-亚氨基庚醇，从而得到 6-叠氮内酯。随后的氢化诱导分子内还原胺化，生成所需的哌啶环系统。

  DOI：

  10.1055/s-1998-1698

文献信息

• [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。
• Piperidine analogues of D-galactose as potent inhibitors of α-galactosidase: Synthesis by stannane-mediated hydroxymethylation of 5-azido-1,4-lactones. Structural relationships between D-galactosidase and L-rhamnosidase inhibitors
  作者：John P. Shilvock、Robert J. Nash、Alison A. Watson、Ana L. Winters、Terry D. Butters、Raymond A. Dwek、David A. Winkler、George W. J. Fleet

  DOI：10.1039/a904145a

  日期：——

  The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono-1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogenation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective α-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of α-galactosidases over naringinase (L-rhamnosidase) are also reported.

  报告了多羟基哌啶脱氧半乳糖苷尻霉素 2、均半乳糖苷尻霉素 7 和 9 以及其他 2,6-亚氨基庚醇衍生物（包括一种 L-altropyranose类似物）的合成。5-Azidoaldono-1,4-lactones 经历了链延伸，通过添加羟甲基锂 18 得到叠氮内酯，羟甲基锂是由受保护的链烷甲醇衍生物 17 反金属化生成的。氢化反应导致叠氮还原，随后进行分子内还原胺化反应，得到哌啶环系统。去保护的亚氨基半乳糖类似物是强效的选择性δ-半乳糖苷酶抑制剂。报告还观察了决定δ-半乳糖苷酶抑制柚皮苷酶（L-鼠李糖酶）选择性的结构特征。
• 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。
• GLYCOSIDASE INHIBITORS AND USES THEREOF
  申请人：Alectos Therapeutics Inc.

  公开号：US20150299122A1

  公开（公告）日：2015-10-22

  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.

  本发明提供了抑制糖苷酶的化合物，该化合物的前药，以及包括该化合物或该化合物的前药的制药组合物。本发明还提供了治疗与O-GlcNA酶的缺乏或过度表达、O-GlcNAc的积累或缺乏有关的疾病和障碍的方法。
• Formulation comprising mutant/s of lysosomal alpha-galactosidase A for the treatment of Fabry disease
  申请人：The Mount Sinai School of Medicine of New York University

  公开号：EP2143420A1

  公开（公告）日：2010-01-13

  A method of enhancing the activity of lysosomal α-Galactosidase A (α-Gal A) in mammalian cells and for treatment of Fabry disease by administration of 1-deoxy-galactonojirimycin and related compounds.

  一种通过服用 1-脱氧-半乳尻霉素和相关化合物来增强哺乳动物细胞溶酶体 α-半乳糖苷酶 A（α-Gal A）活性和治疗法布里病的方法。