1-amino-1,2,5-trideoxy-2,5-imino-D-glucitol | 194288-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-amino-1,2,5-trideoxy-2,5-imino-D-glucitol
• 英文别名: (2R,3R,4R,5S)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 194288-74-9
• 化学式: C₆H₁₄N₂O₃
• 分子量: 162.189
• InChiKey: NJOZFAFEQVQFJI-JGWLITMVSA-N

物化性质

• 沸点：
  373.2±37.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  11
• 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：
  98.7
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-硝基苯基乙酸酯 、 1-amino-1,2,5-trideoxy-2,5-imino-D-glucitol 在 sodium hydroxide 作用下， 生成 N-[[(2R,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]methyl]acetamide
  参考文献：
  名称：

  Intramolecular cyclization of C2 symmetric and meso-iodo amino alcohols: A synthetic approach to azasugars

  摘要：

  C-2 Symmetric and meso-iodo hydroxy ammonium chlorides generated from 2 and 5 have been cyclized under basic conditions to produce various heterocycles chemoselectively, which comprise tetrahydrofurans 7 and 19, piperidines 13, 15 and 21, and pyrrolidines 17 and 18. (C) 1997, Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(96)02403-3
• 作为产物：
  描述：

  (2S,2'S)-<(1R,2R)-1,2-dibenzyloxy-ethan-diyl>bis(1-tert-butoxycarbonyl)-aziridine 在 Amberlite IRA-400 、 sodium 、 三氟乙酸 作用下， 以 二氯甲烷 、 氨 为溶剂， 反应 6.0h， 生成 1-amino-1,2,5-trideoxy-2,5-imino-D-glucitol
  参考文献：
  名称：

  Synthesis and evaluation as glycosidase inhibitors of 2,5-imino- d -glucitol and 1,5-imino- d -mannitol related derivatives

  摘要：

  Selectively functionalized 2,5-imino-D-glucitol and 1,5-imino-D-mannitol derivatives were synthesized and tested as precursors of hydrolytically resistant pseudo-disaccharides. Among them N-acetyl-6-amino-6-deoxy-2,5-imino-D-glucitol (11) and N-acetyl-6-amino-6-deoxy- 1,5-imino-D-mannitol (12) were found potent and specific inhibitors against beta-D-glucosidase and alpha-L-fucosidase, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00267-9

文献信息

• From Natural Product‐Inspired Pyrrolidine Scaffolds to the Development of New Human Golgi α‐Mannosidase II Inhibitors
  作者：Ting‐Jen R. Cheng、Ting‐Hao Chan、En‐Lun Tsou、Shang‐Yu Chang、Wen‐Yi Yun、Pei‐Jung Yang、Ying‐Ta Wu、Wei‐Chieh Cheng

  DOI：10.1002/asia.201300680

  日期：2013.11

  of sixteen natural product‐inspired polyhydroylated pyrrolidine‐based isomeric scaffolds is described. Each scaffold possesses four stereogenic centers and one exo‐aminomethyl moiety, which allows for rapid substituent diversity. To exemplify biological applications, these new privileged scaffolds were used to discover new human Golgi α‐mannosidase II inhibitors. The most potent inhibitor shows competitive

  一点启发：本文描述了系统地制备16种以自然产物为灵感的多氢基吡咯烷基异构支架的方法。每个支架都具有四个立体定位中心和一个外氨基氨基甲基部分，可实现快速的取代基多样性。为了举例说明生物学应用，这些新的特权支架被用于发现新的人类高尔基α-甘露糖苷酶II抑制剂。最有效的抑制剂表现出竞争行为，K i值为24 nM。
• Stereoselective Total Synthesis of Aminoiminohexitols via Carbamate Annulation
  作者：Anna L. Win-Mason、Seino A. K. Jongkees、Stephen G. Withers、Peter C. Tyler、Mattie S. M. Timmer、Bridget L. Stocker

  DOI：10.1021/jo201151b

  日期：2011.12.2

  New methodology for the preparation of a variety of aminoiminohextitols is described. Key in the synthesis is the application of a diastereoselective Strecker reaction and the extension of our carbamate annulation methodology to protected and functionalized alkenylamines. Insight into the effects that the substitution patterns of the alkenylamines have on the diastereoselectivity of the iodocyclization

  描述了制备多种氨基亚氨基己糖醇的新方法。合成中的关键是非对映选择性Strecker反应的应用以及我们氨基甲酸酯环化方法的扩展至受保护和功能化的烯基胺。讨论了烯基胺的取代方式对碘环化和氨基甲酸酯环化的非对映选择性的影响。还提出了对氨基亚氨基己糖醇及其衍生物的糖苷酶抑制活性的评估，其中先前未公开的d - talo异构体显示出对β- d-葡萄糖苷酶的良好选择性抑制。
• Treatment of Fabry disease
  申请人：Academia Sinica

  公开号：US10995067B2

  公开（公告）日：2021-05-04

  Disclosed herein are novel uses of a polyhydroxylated pyrrolidine for the manufacture of a medicament for treating Fabry disease (FD). Accordingly, the present disclosure provides a method of treating a subject having or suspected of having FD. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), a salt, an ester or a solvate thereof, wherein: R1 is H, or C1-3 amine optionally substituted with —COR2; R2 is alkyl or alkene optionally substituted with cycloalkyl or phenyl having at least one substituent selected from the group consisting of, halo, alkyl, haloalkyl, and alkoxyl; so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the FD. According to preferred embodiments of the present disclosure, the compound of formula (I) is a chaperon of a mutated human lysosomal α-galactosidase A (α-Gal A).

  本文公开了一种聚羟基吡咯烷的新用途，用于制造治疗法布里病（FD）的药物。因此，本公开提供了一种治疗法布里病或疑似法布里病受试者的方法。该方法包括以下步骤：向受试者施用治疗有效量的式(I)化合物、其盐、酯或溶液，其中：R1是H，或任选被-COR2取代的C1-3胺；R2是烷基或烯基，任选被环烷基或苯基取代，环烷基或苯基具有至少一个选自由卤代、烷基、卤代烷基和烷氧基组成的组的取代基；从而改善、减轻和/或预防与FD相关的症状。根据本公开的优选实施方案，式（I）化合物是突变的人溶酶体 α-半乳糖苷酶 A（α-Gal A）的合子。
• Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency
  作者：Wei-Chieh Cheng、Jen-Hon Wang、Huang-Yi Li、Sheng-Jhih Lu、Jia-Ming Hu、Wen-Yi Yun、Cheng-Hsin Chiu、Wen-Bin Yang、Yin-Hsiu Chien、Wuh-Liang Hwu

  DOI：10.1016/j.ejmech.2016.07.025

  日期：2016.11

  A unique molecular library consisting of all sixteen synthetic ADMDP (1-aminodeoxy-DMDP) stereo-isomers has been prepared and evaluated for inhibitory activity against alpha-Gal A, and ability to impart thermal stabilization of this enzyme. The results of this testing led us to develop a novel pharmacological chaperone for the treatment of Fabry disease. 3-Epimer ADMDP was found to be an effective pharmacological chaperone, able to rescue alpha-Gal A activity in the lymphoblast of the N215S Fabry patient derived cell line, without impairment of cellular 0-galactosidase activity. When 3-epimer ADMDP was administered with rh-alpha-Gal A (enzyme replacement therapy) for the treatment of Fabry patient-derived cell lines, improvements in the efficacy of rh-alpha-Gal A was observed, which suggests this small molecule can also provide clinical benefit of enzyme replacement therapy in Fabry disease. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Synthesis of 1-amino-1,2,5-trideoxy-2,5-imino-d-mannitol, a novel analogue of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-d-mannitol, via an Amadori rearrangement of 5-azido-5-deoxy-d-glucofuranose
  作者：Tanja M. Wrodnigg、Arnold E. Stütz、Steven G. Withers

  DOI：10.1016/s0040-4039(97)01198-2

  日期：1997.8

  By an Amadori rearrangement of easily available 5-azido-5-deoxy-D-glucofuranose with dibenzylamine and subsequent catalytic hydrogenation of the resulting 5-azido-1-dibenzylamino-1,5-dideoxy-D-fructopyranose, the new 1-amino-1,2,5-trideoxy-2,5-imino-D-mannitol was obtained in only two steps and excellent overall yield. Likewise, other amines and/or other 5-modified hexofuranoses can be used to advantage. The reported rearrangement reaction is a high yielding, convenient and apparently general entry to 1-aminodeoxyketopyranoses modified at C-5, facilitated by the ring enlargement of the aldofuranose to the ketopyranose as an additional driving force. (C) 1997 Elsevier Science Ltd.