2,3,5-tri-O-benzyl-L-ribofuranose

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,5-tri-O-benzyl-L-ribofuranose
• 英文别名: (3S,4S,5S)-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)oxolan-2-ol
• 化学式: C₂₆H₂₈O₅
• 分子量: 420.505
• InChiKey: NAQUAXSCBJPECG-SWFVVNKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3,5-tri-O-benzyl-L-ribofuranose 在 二碳酸二叔丁酯 、 盐酸羟胺 、 氢气 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 33.0h， 生成 (2R,3R,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2016.07.025
• 作为产物：
  描述：

  methyl L-ribofuranoside 在 盐酸 、 sodium hydride 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,3,5-tri-O-benzyl-L-ribofuranose
  参考文献：
  名称：

  氮杂半乳糖-fagomine 的N-烷基化类似物的合成和评估-克雷伯病的潜在药理伴侣†

  摘要：

  制备了七个新颖的六氢哒嗪氮杂半乳糖-fagomine（AGF）的烷基化或酰化类似物，并作为糖苷酶抑制剂进行了研究，目的是提高抑制效力和选择性。发现与克拉伯病有关的半乳糖脑苷脂酶被正丁基N 2-烷基化的AGF有效地抑制。

  DOI：

  10.1039/c6ob01309k

文献信息

• Synthesis of 1,2-<i>cis</i>-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement
  作者：Yves Blériot、Nicolas Auberger、Yerri Jagadeesh、Charles Gauthier、Giuseppe Prencipe、Anh Tuan Tran、Jérôme Marrot、Jérôme Désiré、Arisa Yamamoto、Atsushi Kato、Matthieu Sollogoub

  DOI：10.1021/ol502926f

  日期：2014.11.7

  The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-d-GlcNAc and α-d-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-d-GlcNAc-configured iminosugar was coupled to a glucoside acceptor to yield a novel

  描述了在C-2位带有NHAc基团的1，2-顺式-同氨基糖的合成。制备这些α- d -GlcNAc和α- d -GalNAc模拟物的关键步骤是将β-氨基醇骨架重排应用于zezepane前体。该策略还允许访问天然存在的α-HGJ和α-HNJ。将α - d -GlcNAc-构型的亚氨基糖与葡糖苷受体偶联以产生新的假二糖。初步的糖苷酶抑制评估表明，α - d -GalNAc构型的同亚氨基糖是一种有效的选择性α- N-乙酰半乳糖苷酶抑制剂。
• Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities
  作者：Kuniaki Tatsuta、Shozo Miura、Shigeru Ohta、Hiroki Gunji

  DOI：10.1016/0040-4039(94)02460-s

  日期：1995.2

  De-branched nagstatin and its analogs have been synthesized from protected L-ribo- and xylofuranoses through the inter- and intra-molecular nucleophilic reactions with the imidazole moieties.

  去支化的那格他汀及其类似物已经通过与咪唑部分的分子间和分子内亲核反应，从受保护的L-核糖基和木糖基呋喃糖合成。
• The Total Synthesis of a Glycosidase Inhibitor, Nagstatin
  作者：Kuniaki Tatsuta、Shozo Miura、Hiroki Gunji

  DOI：10.1246/bcsj.70.427

  日期：1997.2

  A glycosidase inhibitor, nagstatin, has been synthesized from protected L-ribofuranose through the inter- and intra-molecular nucleophilic reactions of the imidazole moieties and the regioselective introduction of a carboxymethyl group.

  通过咪唑部分的分子间和分子内亲核反应和羧甲基基团的区域选择性引入，已从受保护的 L-呋喃核糖合成糖苷酶抑制剂纳格他汀。
• Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4]triazine C-nucleosides
  作者：Qingfeng Li、Elisabetta Groaz、Joana Rocha-Pereira、Johan Neyts、Piet Herdewijn

  DOI：10.1016/j.ejmech.2020.112198

  日期：2020.6

  Synthetic nucleoside analogues characterized by a C-C anomeric linkage form a family of promising therapeutics against infectious and malignant diseases. Herein, C-nucleosides comprising structural variations at the sugar and nucleobase moieties were examined for their ability to inhibit both murine and human norovirus RNA-dependent RNA polymerase (RdRp). We have found that the combination of 4-amino-pyrrolo[2

  以CC异头键为特征的合成核苷类似物形成了一个有前途的针对传染性和恶性疾病的疗法。本文中，检查了在糖和核碱基部分包含结构变异的C-核苷抑制鼠和人诺如病毒RNA依赖性RNA聚合酶（RdRp）的能力。我们发现4-氨基-吡咯并[2,1-f] [1,2,4]三嗪及其7-卤代同族与d-核糖或2'-C-甲基-d-核糖的组合该单元产生了对鼠诺如病毒（MNV）具有良好抗病毒活性的类似物，尽管其具有明显的细胞毒性。在该系列中，4-氮杂-7,9-二氮杂叠氮腺苷在人诺如病毒（HuNoV）复制子测定中的EC50 = 0.015μM时特别保留了强大的抗病毒作用。
• [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。