(2R,3R,4S,5R)-2,5-双(羟甲基)吡咯烷-3,4-二醇 | 172823-15-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (2R,3R,4S,5R)-2,5-双(羟甲基)吡咯烷-3,4-二醇
• 英文名称: 2,5-dideoxy-2,5-imino-D-altritol
• 英文别名: 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine；(2R,3S,4R,5R)-2,5-bis(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 172823-15-3
• 化学式: C₆H₁₃NO₄
• 分子量: 163.174
• InChiKey: PFYHYHZGDNWFIF-KAZBKCHUSA-N

物化性质

• 沸点：
  395.9±37.0 °C(Predicted)
• 密度：
  1.408±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 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：
  93
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2,5-双(羟甲基)吡咯烷-3,4-二醇 在 盐酸 作用下， 生成 2,5-dideoxy-2,5-imino-D-altritol hydrochloride
  参考文献：
  名称：

  通过非对映选择性还原胺化和氨基甲酸酯环化反应合成分子伴侣2,5-二脱氧-2,5-亚氨基-d-麦芽糖醇

  摘要：

  所述亚氨基糖-2,5-二脱氧-2,5-亚氨基d -altritol（DIA，2）是α半乳糖苷酶A的强有力的竞争抑制剂，并表现出很大希望作为治疗法布里病药理学伴侣。尽管如此，DIA的合成仍需要优化。因此，我们报告了7个步骤中DIA的总合成以及从容易获得的d-塔格糖中获得22％的总收率。这是迄今为止DIA最短，最有效的合成方法，是我们合成策略中的关键步骤，包括非对映选择性还原胺化和I 2介导的氨基甲酸酯环化。

  DOI：

  10.1016/j.tet.2018.01.011
• 作为产物：
  描述：

  D-塔格糖 在 咪唑 、 硫酸 、 ammonium acetate 、 碘 、 sodium cyanoborohydride 、 碳酸氢钠 、 copper(II) sulfate 、 三苯基膦 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 72.5h， 生成 (2R,3R,4S,5R)-2,5-双(羟甲基)吡咯烷-3,4-二醇
  参考文献：
  名称：

  通过非对映选择性还原胺化和氨基甲酸酯环化反应合成分子伴侣2,5-二脱氧-2,5-亚氨基-d-麦芽糖醇

  摘要：

  所述亚氨基糖-2,5-二脱氧-2,5-亚氨基d -altritol（DIA，2）是α半乳糖苷酶A的强有力的竞争抑制剂，并表现出很大希望作为治疗法布里病药理学伴侣。尽管如此，DIA的合成仍需要优化。因此，我们报告了7个步骤中DIA的总合成以及从容易获得的d-塔格糖中获得22％的总收率。这是迄今为止DIA最短，最有效的合成方法，是我们合成策略中的关键步骤，包括非对映选择性还原胺化和I 2介导的氨基甲酸酯环化。

  DOI：

  10.1016/j.tet.2018.01.011
• 作为试剂：
  描述：

  4-硝基苯基-α-D-吡喃半乳糖苷 在 human lysosome α-galactosidase A 、 (2R,3R,4S,5R)-2,5-双(羟甲基)吡咯烷-3,4-二醇 作用下， 生成 对硝基苯酚
  参考文献：
  名称：

  2,5-Dideoxy-2,5-imino-d-altritol as a new class of pharmacological chaperone for Fabry disease

  摘要：

  Chromatographic separation of the extract from roots of Adenophora triphylla resulted in the isolation of two pyrrolidines, six piperidines, and two piperidine glycosides. The structures of new iminosugars were elucidated by spectroscopic methods as 2,5-dideoxy-2,5-imino-D-altritol (DIA) (2), beta-1-C-butenyl-1-deoxygalactonojirimycin (8), 2,3-dideoxy-beta-1-C-ethyl-1-deoxygalactonojirimycin (9), and 6-O-beta-D-glucopyranosyl-2,3-dideoxy-beta-1-C-ethyl-1-deoxygalactonojirimycin (10). beta-1-C-Butyl-1-deoxygalactonojirimycin (7) and compound 8 were found to be better inhibitors of alpha-galactosidase than N-butyl-1-deoxygalactonojirimycin. The present work elucidated that DIA was a powerful competitive inhibitor of human lysosome alpha-galactosidase A (alpha-Gal A) with a K(i) value of 0.5 mu M. Furthermore, DIA improved the thermostability of alpha-Gal A in vitro and increased intracellular alpha-Gal A activity by 9.6-fold in Fabry R301Q lymphoblasts after incubation for 3 days. These experimental results suggested that DIA would act as a specific pharmacological chaperone to promote the smooth escape from the endoplasmic reticulum (ER) quality control system and to accelerate transport and maturation of the mutant enzyme. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.048

文献信息

• On the Asymmetric Induction in Proline-Catalyzed Aldol Reactions: Reagent-Controlled Addition Reactions of 2,2-Dimethyl-1,3-dioxane-5-one to Acyclic Chiral α-Branched Aldehydes
  作者：Jasna Marjanovic Trajkovic、Vesna Milanovic、Zorana Ferjancic、Radomir N. Saicic

  DOI：10.1002/ejoc.201701073

  日期：2017.11.9

  Proline-catalyzed aldol addition reactions of 2,2-dimethyl-1,3-dioxane-5-one to chiral aldehydes proceed under reagent stereocontrol (in both matched and mismatched cases) if aldehyde α-oxy or α-amino substituents are acyclic. For cyclic substituents, the stereochemical outcome of the aldolization in mismatched cases is difficult to predict.

  如果醛的α-氧基或α-氨基取代基是无环的，则在试剂立体控制下（在匹配和不匹配的情况下），脯氨酸催化的2，2-二甲基-1，3-二恶烷-5-酮与手性醛的羟醛加成反应。对于环状取代基，在不匹配的情况下醛醇缩合的立体化学结果很难预测。
• Enantiospecific syntheses of deoxymannojirimycin, fagomine and 2r,5r-dihydroxymethyl-3r,4r-dihydroxypyrrolidine from D-glucose
  作者：George W.J. Fleet、Paul W. Smith

  DOI：10.1016/s0040-4039(00)99073-7

  日期：1985.1

  Methyl 2-azido-3-O-benzyl-2-deoxy-α-D-mannofuranoside (4), readily available from D-glucose, is a common intermediate in the enantiospecific syntheses of deoxymannojirimycin [1,5-dideoxy-1,5-imino-D-mannitol](l), fagomine [1,2,5-trideoxy-1,5-imino-D- arabino hexitol] (2) and 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (3); these syntheses establish the absolute configurations of (2) and (3).

  易于从D-葡萄糖获得的甲基2-叠氮基-3-O-苄基-2-脱氧-α-D-甘露呋喃糖苷（4）是脱氧甘露糖霉素[1,5-dideoxy-1， 5-亚氨基-D-甘露糖醇]（l），花青碱[1,2,5-三苯氧基-1,5-亚氨基-D-阿拉伯己糖醇]（2）和2R，5R-二羟基甲基-3R，4R-二羟基吡咯烷（3 ）; 这些合成建立了（2）和（3）的绝对构型。
• Synthesis and enzymatic evaluation of five-membered iminocyclitols and a pseudodisaccharide
  作者：Chikako Saotome、Yoshimi Kanie、Osamu Kanie、Chi-Huey Wong

  DOI：10.1016/s0968-0896(00)00170-x

  日期：2000.9

  Described here are the synthesis of five-membered iminocyclitols with galacto-configuration and a pseudodisaccharide, and their inhibitory activities against beta-galactosyltransferase, beta-galactosidase and alpha-mannosidase.

  这里描述的是具有半乳糖构型和假二糖的五元亚氨基环糖醇的合成及其对β-半乳糖基转移酶，β-半乳糖苷酶和α-甘露糖苷酶的抑制活性。
• [EN] GLYCOSIDASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DES GLYCOSIDASES ET LEURS UTILISATIONS
  申请人：ALECTOS THERAPEUTICS INC

  公开号：WO2014032188A1

  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化合物的前药的药物组合物。该发明还提供了治疗与O-GlcNA酶缺乏或过度表达、O-GlcNAc的积累或缺乏相关的疾病和障碍的方法。
• [EN] TREATMENT OF FABRY DISEASE<br/>[FR] TRAITEMENT DE LA MALADIE DE FABRY
  申请人：ACADEMIA SINICA

  公开号：WO2017222881A1

  公开（公告）日：2017-12-28

  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).

  本文揭示了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患有或疑似患有FD的受试者的方法。该方法包括步骤，向受试者施用化合物I式，其盐、酯或溶剂化物的治疗有效量，其中：R1是H，或C1-3胺，可选地取代为-COR2；R2是烷基或烯烃，可选地取代为环烷基或苯基，其至少有一个取代基选自卤素，烷基，卤代烷基和烷氧基的群体；以缓解、减轻和/或预防与FD相关的症状。根据本公开的优选实施例，化合物I式是人类溶酶体α-半乳糖苷酶A（α-Gal A）的突变体的伴侣蛋白。