(3R,3aS,5R,6R,7R,7aS)-3-acetamido-6,7-di(benzyloxy)-5-(benzyloxymethyl)-3-(hydroxymethyl)-2-oxo-1,3a,5,6,7,7a-hexahydropyran[3,2-b]pyrrole

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R,3aS,5R,6R,7R,7aS)-3-acetamido-6,7-di(benzyloxy)-5-(benzyloxymethyl)-3-(hydroxymethyl)-2-oxo-1,3a,5,6,7,7a-hexahydropyran[3,2-b]pyrrole
• 英文别名: N-[(3R,3aS,5R,6R,7R,7aS)-3-(hydroxymethyl)-2-oxo-6,7-bis(phenylmethoxy)-5-(phenylmethoxymethyl)-1,3a,5,6,7,7a-hexahydropyrano[3,2-b]pyrrol-3-yl]acetamide
• 化学式: C₃₂H₃₆N₂O₇
• 分子量: 560.647
• InChiKey: MVFOTHSTLUOPTQ-VHYWMORQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R,3aS,5R,6R,7R,7aS)-3-acetamido-6,7-di(benzyloxy)-5-(benzyloxymethyl)-3-(hydroxymethyl)-2-oxo-1,3a,5,6,7,7a-hexahydropyran[3,2-b]pyrrole 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 以54%的产率得到(3R,3aS,5R,6R,7R,7aR)-3-acetamido-6,7-dihydroxy-3,5-bis(hydroxymethyl)-2-oxo-1,3a,5,6,7,7a-hexahydropyran[3,2-b]pyrrole
  参考文献：
  名称：

  A Double Diastereoselective Michael-Type Addition as an Entry to Conformationally Restricted Tn Antigen Mimics

  摘要：

  A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-D-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their C-4(1) chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.

  DOI：

  10.1021/jo4019396
• 作为产物：
  描述：

  3,4,6-tri-O-benzyl-2-nitro-D-galactal 在 吡啶 、 盐酸 、 dihydrogen hexachloroplatinate 、 氢气 、 sodium methylate 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， -78.0~40.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 (3R,3aS,5R,6R,7R,7aS)-3-acetamido-6,7-di(benzyloxy)-5-(benzyloxymethyl)-3-(hydroxymethyl)-2-oxo-1,3a,5,6,7,7a-hexahydropyran[3,2-b]pyrrole
  参考文献：
  名称：

  A Double Diastereoselective Michael-Type Addition as an Entry to Conformationally Restricted Tn Antigen Mimics

  摘要：

  A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-D-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their C-4(1) chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.

  DOI：

  10.1021/jo4019396

文献信息

• Conformationally-locked C-glycosides: tuning aglycone interactions for optimal chaperone behaviour in Gaucher fibroblasts
  作者：C. D. Navo、F. Corzana、E. M. Sánchez-Fernández、J. H. Busto、A. Avenoza、M. M. Zurbano、E. Nanba、K. Higaki、C. Ortiz Mellet、J. M. García Fernández、J. M. Peregrina

  DOI：10.1039/c5ob02281a

  日期：——

  provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound Ambroxol®.

  合成了一系列基于3-氨基吡喃并[3,2 - b ]吡咯-2（1 H）-one（APP）支架的构象锁定的C-糖苷。关键步骤涉及作者先前发表的将立体丝氨酸等效的C-亲核体完全立体控制的C -Michael加成到三-O-苄基-2-硝基-D-半乳糖上。迈克尔加合物的立体选择性转化使我们能够合成具有单或双天线的糖苷配基部分和不同拓扑结构的化合物。体外筛选显示了牛肝β-葡萄糖苷酶/β-半乳糖苷酶的高度选择性抑制以及溶酶体糖苷酶中糖苷配基中带有棕榈酰基链的化合物对人β-葡萄糖脑苷脂酶的特异性抑制，抑制力的显着依赖性取决于其数量和位置。分子动力学模拟突出了疏水取代基的最佳取向以确保有效的非糖苷相互作用的最重要意义，这对于结合亲和力至关重要。该结果为从中性至酸性pH时APP化合物抑制能力的大幅降低提供了理论依据。在具有纯合N370S和F213I突变的Gaucher成纤维细胞中，发现最佳候选物具有药理分子伴侣的作用，
• A Double Diastereoselective Michael-Type Addition as an Entry to Conformationally Restricted Tn Antigen Mimics
  作者：Carlos Aydillo、Claudio D. Navo、Jesús H. Busto、Francisco Corzana、María M. Zurbano、Alberto Avenoza、Jesús M. Peregrina

  DOI：10.1021/jo4019396

  日期：2013.11.1

  A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-D-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their C-4(1) chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.