(2S,3S,4R)-3,4-bis(benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-2H-pyrrole-1-oxide | 1105054-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3S,4R)-3,4-bis(benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-2H-pyrrole-1-oxide
• 英文别名: (2S,3S,4R)-1-oxido-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)-3,4-dihydro-2H-pyrrol-1-ium
• CAS: 1105054-63-4
• 化学式: C₂₆H₂₇NO₄
• 分子量: 417.505
• InChiKey: FYVRCXABOYBHKY-NXCFDTQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  56.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S,4R)-3,4-bis(benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-2H-pyrrole-1-oxide 在 二碳酸二叔丁酯 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 7.0h， 生成 (2R,3R,4S,5S)-2-(aminomethyl)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)pyrrolidine
  参考文献：
  名称：

  Pochonicine 的吡咯烷单环类似物及其立体异构体的合成：追求简化的结构和有效的 β-N-乙酰己糖胺酶抑制

  摘要：

  由四对多羟基化环硝酮对映体合成了十对 Pochonicine 的吡咯烷类似物及其立体异构体。在十种 N-乙酰氨基吡咯烷类似物中，只有具有 2,5-二脱氧-2,5-亚氨基-d-甘露醇 (DMDP) 和 Pochonicine (1) 构型的化合物显示出对 β-N-乙酰己糖胺酶 (β-HexNAcases) 的有效抑制作用;而1-氨基类似物几乎失去了对测试酶的所有抑制作用。测定结果揭示了 N-乙酰氨基的重要性以及此类抑制剂所需的吡咯烷环可能的正确构型。

  DOI：

  10.3390/molecules25071498
• 作为产物：
  描述：

  C₄₂H₄₇NO₅Si 在 甲基磺酰氯 、 三乙胺 、 四丁基氟化铵 作用下， 以 二氯甲烷 、 四氢呋喃 、 甲苯 为溶剂， 反应 0.5h， 生成 (2S,3S,4R)-3,4-bis(benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-2H-pyrrole-1-oxide
  参考文献：
  名称：

  A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP

  摘要：

  A practical method for the synthesis of five-membered iminocyclitols, pyrrolidine alkaloids bearing multiple hydroxyl substituents, has been developed. All of the eight key intermediates, enantiopure tri-O-benzyl cyclic nitrones, are prepared from four cheap, readily available D-aldopentoses. The nucleophilic addition of cyclic nitrones with vinyl magnesium chloride and TMSCN shows high 2,3-trans stereoselectivity. To construct the 2,3-cis configurations, inversion of the C-2 nitrile group is achieved via an elimination-reduction sequence. Using this approach, five isomers of DMDP and six isomers of ADMDP are prepared efficiently. In the biological evaluation, iminocyclitol 27 is a new and potent inhibitor against beta-hexosaminidase with an IC50 value of 0.2 mu M. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.10.096

文献信息

• [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。
• 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.