(1R)-5N,6O-oxomethylidenenojirimycin | 260790-65-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (1R)-5N,6O-oxomethylidenenojirimycin
• 英文别名: (5R,6R,7S,8R,8aR)-5,6,7,8-tetrahydroxy-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-3-one
• CAS: 260790-65-6
• 化学式: C₇H₁₁NO₆
• 分子量: 205.167
• InChiKey: GAEMVFBCSZKQAJ-VFUOTHLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R)-5N,6O-oxomethylidenenojirimycin 在 三氟甲磺酸三甲基硅酯 、 乙酸肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 cyclohexyl 2,3,4-tri-O-acetyl-6-O,N-carbonylidene-5-deoxy-1,5-imino-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  5-Amino-5-Deoxy-1-Thioglucopyranosides-Synthesis of Thioglycoside Derivatives of Nojirimycin

  摘要：

  N-Benzyloxycarbonyl-protected 5-amino-5-deoxyglucofuranose derivative 1 could be readily transformed into 6-O, N-carbonylidene nojirimycin 3 which afforded the corresponding piperidinosyl trichloroacetimidate 6. This compound turned out to be a versatile piperidinosyl donor. Reaction with various mercaptans as accepters in the presence of TMSOTf as catalyst gave 5-aza-1-thioglucopyranosides 7a-c, 9, and 13 which were successfully deprotected.

  DOI：

  10.1080/07328300008544110
• 作为产物：
  描述：

  5-Benzyloxycarbonylamino-5-deoxy-1,2-O-isopropylidene-α-D-glucofuranose 在 sodium hydroxide 、 IRA-420 (OH^-) 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 14.0h， 生成 (1R)-5N,6O-oxomethylidenenojirimycin
  参考文献：
  名称：

  5-Amino-5-Deoxy-1-Thioglucopyranosides-Synthesis of Thioglycoside Derivatives of Nojirimycin

  摘要：

  N-Benzyloxycarbonyl-protected 5-amino-5-deoxyglucofuranose derivative 1 could be readily transformed into 6-O, N-carbonylidene nojirimycin 3 which afforded the corresponding piperidinosyl trichloroacetimidate 6. This compound turned out to be a versatile piperidinosyl donor. Reaction with various mercaptans as accepters in the presence of TMSOTf as catalyst gave 5-aza-1-thioglucopyranosides 7a-c, 9, and 13 which were successfully deprotected.

  DOI：

  10.1080/07328300008544110

文献信息

• Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties
  作者：Elena M. Sánchez-Fernández、Raquel García-Hernández、Francisco Gamarro、Ana I. Arroba、Manuel Aguilar-Diosdado、José M. Padrón、José M. García Fernández、Carmen Ortiz Mellet

  DOI：10.3390/molecules26247501

  日期：——

  key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp2-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position.

  sp 2 -亚氨基糖糖脂 (sp 2 -IGLs) 代表糖缀合物模拟物的综合家族，包括单糖样糖基部分，其中假酰胺型氮取代碳水化合物的环内氧原子和锚定在假异头位置的轴向脂质链. 这些结构特征的结合使它们成为治疗各种疾病的有希望的候选者，从癌症和炎症性疾病到寄生虫感染。与推定的 sp 2 -杂化 N 原子相关的加剧的异头效应赋予 sp 2 -IGLs 化学和酶稳定性，并保证关键糖缀合步骤中的总 α-异头立体选择性。各种各样O-、N-、C-和S-假糖苷类在糖基构型和脂质性质方面不同，之前已经制备和评估过。在这里，我们通过报告合成具有在糖苷位置结合硒的双环 (5 N ,6 O-氧亚甲基) 野尻霉素 (ONJ) 核心的 α- d - 葡萄糖配置类似物来扩展 sp 2 -IGL的化学空间。三种不同情况下的构效关系研究，即癌症、利什曼病和炎症，表明 sp 2 -IGLs 的治疗潜力高度依赖于脂质链的长度（线性脂肪族
• Influence of the configurational pattern of sp2-iminosugar pseudo N-, S-, O- and C-glycosides on their glycoside inhibitory and antitumor properties
  作者：Elena M. Sánchez-Fernández、Rita Gonçalves-Pereira、Rocío Rísquez-Cuadro、Gabriela B. Plata、José M. Padrón、José M. García Fernández、Carmen Ortiz Mellet

  DOI：10.1016/j.carres.2016.01.006

  日期：2016.6

  sp(2)-iminosugar representatives exhibiting significant growth inhibition potencies were identified in all three configurationally different types of compounds studied, namely α-d-gluco, α-d-manno and α-d-galacto glycoside analogs. Interestingly, none of the compounds affected viability and mortality of normal cells at the used concentrations. Altogether, the results strongly suggest that the anticancer activity

  据报道，与nojirimycin，mannojirimycin和galactonojirimycin相关的环状氨基甲酸酯型sp（2）-亚氨基糖N-，S-，O-和C-辛基伪糖苷的合成全都具有α-伪异头构型。通过与甲醇中的辛胺反应，可以直接从相应的还原性sp（2）-亚氨基糖前体直接获得gem-diamine-type N-pseudoglycosides，而过-O-乙酰基或1-氟衍生物用作拟糖基供体分别是S-伪糖苷或O-和C-伪糖苷。评估它们对一组糖苷酶的抑制性能证明了选择性概况，其选择性很大程度上取决于糖苷键的构型和性质。相反，确定的针对一组肿瘤细胞系的抗增殖活性在很大程度上与sp（2）-亚氨基糖部分中羟基的相对方向无关。实际上，在研究的所有三种构型不同类型的化合物（即α-d-葡萄糖，α-d-甘露聚糖和α-d-半乳糖苷类似物）中均已鉴定出显示出显着的生长抑制能力的sp（2）-亚氨基糖代表。有
• Synthesis of Multibranched Australine Derivatives from Reducing Castanospermine Analogues through the Amadori Rearrangement of <i>gem</i>-Diamine Intermediates: Selective Inhibitors of β-Glucosidase
  作者：Elena M. Sánchez-Fernández、Eleuterio Álvarez、Carmen Ortiz Mellet、José M. García Fernández

  DOI：10.1021/jo5025283

  日期：2014.12.5

  A practical one-pot synthesis of bi- and triantennated australine analogues from a pivotal sp2-iminosugar-type reducing castanospermine precursor is reported. The transformation involves a gem-diamine intermediate that undergoes the indolizidine → pyrrolizidine Amadori-type rearrangement and proceeds under strict control of the generalized anomeric effect to afford a single diastereomer. The final

  据报道，从枢轴的sp 2-亚氨基糖型还原的粟精胺前体中，实际的一锅法合成双和三天线的澳大林碱类似物。该转化涉及一种宝石-二胺中间体，该中间体经历了吲哚并idine→吡咯并idine的Amadori-型重排，并在广义的异头作用的严格控制下进行，从而得到单一的非对映异构体。最终化合物可作为β-葡萄糖苷酶的选择性竞争性抑制剂，并且有望成为高雪氏病药理伴侣的候选药物。
• Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies
  作者：Elena M. Sánchez-Fernández、Ma Isabel García-Moreno、Ana I. Arroba、Manuel Aguilar-Diosdado、José M. Padrón、Raquel García-Hernández、Francisco Gamarro、Santos Fustero、José-Emilio Sánchez-Aparicio、Laura Masgrau、José Manuel García Fernández、Carmen Ortiz Mellet

  DOI：10.1016/j.ejmech.2019.111604

  日期：2019.11

  often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response. The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously

  免疫调节性糖脂（其中的α-半乳糖基神经酰胺（KRN7000）是一个标志性的例子）在从癌症和感染到自身免疫性疾病或神经退行性疾病的各种疾病中均显示出强大的治疗潜力。这些通道的主要困难是它们经常引起细胞因子风暴，其中包括相互拮抗并负面影响免疫反应的促炎和抗炎介质。控制糖苷化反应中立体化学结果的固有困难阻碍了具有更窄的细胞因子分泌诱导能力的类似物的合成，特别是如果靶向α-异头物，这将严重阻碍药物优化策略。在这里，我们显示了用sp 2代替单糖甘氨酸-亚氨基糖的糖模拟物部分允许访问N-连接的sp 2-亚氨基糖的糖脂（sp 2-IGLs），只需一步即可完全控制α-立体异构，无需保护基团或糖苷化促进剂。考虑到与主p38丝裂原活化蛋白激酶（p38 MAPK）的脂质结合位点的结合，从而易于掺入各种长度的多氟烷基片段来修饰脂质尾巴，从而以细胞背景依赖性的方式极化免疫反应。已经在不同的细胞试验中评估了这些化合物
• Generalized Anomeric Effect in <i>gem</i>-Diamines: Stereoselective Synthesis of α-<i>N</i>-Linked Disaccharide Mimics
  作者：Elena M. Sánchez-Fernández、Rocío Rísquez-Cuadro、Matilde Aguilar-Moncayo、M. Isabel García-Moreno、Carmen Ortiz Mellet、José M. García Fernández

  DOI：10.1021/ol901125n

  日期：2009.8.6

  The orbital (negative hyperconjugation) contribution to the generalized anomeric effect is highly increased in bicyclic gem-diamines with a pseudoamide-type endocyclic nitrogen atom, which has been exploited for the stereoselective synthesis of configurationally stable α-N-linked azadisaccharide heteroanalogues of the natural disaccharides maltose and isomaltose as aglycon-sensitive inhibitors of isomaltase

  在具有假酰胺型内环氮原子的双环宝石-二胺中，轨道（负超共轭）对广义异头作用的贡献大大增加，已被用于立体选择性合成天然构型稳定的α- N-连接的氮杂二糖杂类似物二糖麦芽糖和异麦芽糖作为糖异糖苷酶的糖苷配基敏感抑制剂。