5-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)tetrazole | 706784-62-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)tetrazole
• 英文别名: [(2R,3R,4R,5S,6S)-3,4,5-tribenzoyloxy-6-(2H-tetrazol-5-yl)oxan-2-yl]methyl benzoate
• CAS: 706784-62-5
• 化学式: C₃₅H₂₈N₄O₉
• 分子量: 648.629
• InChiKey: MAZSZUSBYNYRQL-CMPUJJQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  48.0
• 可旋转键数：
  10.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  168.89
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  5-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)tetrazole 在 sodium azide 、 sodium methylate 、 copper(II) sulfate 、 维生素 C 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 2-(β-D-glucopyranosyl)-5-(4'-methoxycarbonyl-1',2',3'-triazol-1'-methyl)-1,3,4-oxadiazole
  参考文献：
  名称：

  Synthesis of variously coupled conjugates of d-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase

  摘要：

  5-(O-Perbenzoylated-beta-D-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-beta-D-glucopyranosyl cyanide by Bu3SnN3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated-beta-D-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and asides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplen protocol, beta-D-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3-triazole, beta-D-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and beta-D-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4-oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(beta-D-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: K-i = 854 mu M, 2-(beta-D-glucopyranosyl)-5-[1-(naphthalen-2-yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: K-i = 745 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.03.004
• 作为产物：
  描述：

  (2R,3R,4R,5S,6S)-2-[(苯甲酰氧基)甲基]-6-氰基四氢-2H-吡喃-3,4,5-三基三苯甲酸酯 在 ammonium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以94%的产率得到5-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)tetrazole
  参考文献：
  名称：

  Synthesis and structure–activity relationships of C-glycosylated oxadiazoles as inhibitors of glycogen phosphorylase

  摘要：

  A series of per-O-benzoylated 5-beta-D-glucopyranosyl-2-substituted-1,3,4-oxadiazoles was prepared by acylation of the corresponding 5-(beta-D-glucopyranosyl) tetrazole. As an alternative, oxidation of 2,6-anhydro-aldose benzoylhydrazones by iodobenzene I, I-diacetate afforded the same oxadiazoles. 1,3-Dipolar cycloaddition of nitrile oxides to per-O-benzoylated beta-D-glucopyranosyl cyanide gave the corresponding 5-beta-D-glucopyranosyl-3-substituted-1,2,4-oxadiazoles. The O-benzoyl protecting groups were removed by base-catalyzed transesterification. The 1,3,4-oxadiazoles were practically inefficient as inhibitors of rabbit muscle glycogen phosphorylase b while the 1,2,4-oxadiazoles displayed inhibitory activities in the micromolar range. The best inhibitors were the 5-beta-D-glucopyranosyl-3-(4-methylphenyl-and -2-naphthyl)- 1,2,4-oxadiazoles (K-i = 8.8 and 11.6 mu M, respectively). A detailed analysis of the structure-activity relationships is presented. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.036

文献信息

• Coupling of <i>N</i>-tosylhydrazones with tetrazoles: synthesis of 2-β-<scp>d</scp>-glycopyranosylmethyl-5-substituted-2<i>H</i>-tetrazole type glycomimetics
  作者：Tímea Kaszás、Ivett Cservenyák、Éva Juhász-Tóth、Andrea E. Kulcsár、Paola Granatino、Ulf J. Nilsson、László Somsák、Marietta Tóth

  DOI：10.1039/d0ob02248a

  日期：——

  The first tosylhydrazone-tetrazole coupling provides a straightforward access to a new type of glycomimetics with exclusive regioselectivity.

  第一次甲磺酰肼-四唑偶联反应为一种具有独特区域选择性的新型糖类模拟物提供了一种直接途径。
• Glycosylation with ulosonates under Mitsunobu conditions: scope and limitations
  作者：Nándor Kánya、Sándor Kun、Gyula Batta、László Somsák

  DOI：10.1039/d0nj03044a

  日期：——

  A systematic study was performed by using Mitsunobu conditions (diethyl azodicarboxylate, Ph3P or n-Bu3P in THF or CH3CN) for glycosylations with methyl 3,4,5,7-tetra-O-benzoyl-α-D-gluco-hept-2-ulopyranosonate. From a set of 47 O-, N-, S- and C-nucleophiles, phenols and N-hydroxy compounds with a pKa of 5–8, phthalimide, benzotriazole, 6-chloropurine, an oxazolidinedione and several tetrazoles with

  通过使用Mitsunobu条件（在THF或CH 3 CN中的偶氮二羧酸二乙酯，Ph 3 P或n -Bu 3 P ）进行甲基，3,4,5,7-四-O-苯甲酰基-α- D的糖基化研究-葡萄糖-庚-2- ulopyranosonate。选自47种O-，N-，S-和C-亲核试剂，酚和N-羟基化合物，其ap K a为5-8，邻苯二甲酰亚胺，苯并三唑，6-氯嘌呤，恶唑烷二酮和若干具有ap K a的四唑苯酚的比例为4-8，而苯酚以中等到非常高的产率提供了相应的产物，而C-亲核试剂则没有反应性。对三卤代乙酰苯胺进行O-糖基化反应，得到O-糖基-N-芳基三卤代乙酰亚胺酸酯，这是常规的O-亚氨基化无法制备的。所有反应都是高度立体选择性的，仅产生β（D）异构体。用甲基（5-乙酰氨基-4,7,8,9-四- ø -乙酰基-3,5-二脱氧d -甘油基- d -半乳-2-壬基吡喃二酮酸）酚和苯并三唑生成了预期的产物，但
• Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
  作者：Sándor Kun、Éva Bokor、Ádám Sipos、Tibor Docsa、László Somsák

  DOI：10.3390/molecules23030666

  日期：——

  ,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-d-glucopyranosyl ethynes and aryl azides. 1-β-d-Gluco-pyranosyl-4-phenyl imidazole was obtained in a glycosylation of 4(5)-phenylimidazole with O-peracetylated α-d-glucopyranosyl bromide. C-β-d-Glucopyranosyl-N-substituted-tetrazoles were synthesized by alkylation/arylation of O-perbenzoylated

  本研究的目的是拓宽糖原磷酸化酶的C-和N-β-d-吡喃葡萄糖基唑类抑制剂的结构-活性关系。通过在O-过苄基化或O-过乙酰化的β-d-吡喃葡萄糖基乙炔与芳基叠氮化物之间进行铜催化的叠氮化物-炔烃环加成反应，制得1-芳基-4-β-d-葡萄糖-吡喃葡萄糖基-1,2,3-三唑。在4-（5）-苯基咪唑与O-过乙酰化的α-d-吡喃葡萄糖基溴化物的糖基化反应中获得了1-β-d-葡糖基-吡喃基-4-苯基咪唑。通过O-过苯甲酰化的5-β-d-吡喃葡萄糖基-四唑的烷基化/芳基化反应或由2,6-脱水庚糖甲苯磺酰and和槟榔重氮盐合成C-β-d-戊二糖基-N-取代的四唑。将5-取代的四唑通过O-过乙酰化的α-d-吡喃葡萄糖基溴化物糖基化，得到N-β-d-吡喃葡萄糖基-C取代的四唑。标准脱保护得到测试化合物，其针对兔肌肉糖原磷酸化酶b进行了测定。多数化合物被证明是无活性的，最好的抑制剂是2-β-d-吡喃葡萄糖基-5-苯基四唑（IC50
• A multidisciplinary study of 3-(β- d -glucopyranosyl)-5-substituted-1,2,4-triazole derivatives as glycogen phosphorylase inhibitors: Computation, synthesis, crystallography and kinetics reveal new potent inhibitors
  作者：Sándor Kun、Jaida Begum、Efthimios Kyriakis、Evgenia C.V. Stamati、Thomas A. Barkas、Eszter Szennyes、Éva Bokor、Katalin E. Szabó、George A. Stravodimos、Ádám Sipos、Tibor Docsa、Pál Gergely、Colin Moffatt、Myrto S. Patraskaki、Maria C. Kokolaki、Alkistis Gkerdi、Vassiliki T. Skamnaki、Demetres D. Leonidas、László Somsák、Joseph M. Hayes

  DOI：10.1016/j.ejmech.2018.01.095

  日期：2018.3

  inhibitors with Ki's < 10 μM (AU-ROC = 0.86). Accordingly, in silico screening of 2335 new analogues exploiting the ZINC docking database was performed and nine predicted candidates selected for synthesis. The compounds were prepared in O-perbenzoylated forms by either ring transformation of 5-β-d-glucopyranosyl tetrazole by N-benzyl-arenecarboximidoyl chlorides, ring closure of C-(β-d-glucopyranosyl)formamidrazone

  已经揭示了3-（β- d-葡糖基葡糖基）-5-取代的1,2,4-三唑是开发有效的糖原磷酸化酶（GP）抑制剂的有效支架，但是其效力对其本质非常敏感。烷基/芳基5-取代基（Kun等人，Eur.J.Med.Chem.2014，76，567）。对于这些配体的训练集，量子力学极化的配体对接（QM-PLD）表现出良好的潜力，可以识别出更大的功效差异（预测指数PI = 0.82）和K i <10μM的有效抑制剂（AU-ROC） = 0.86）。因此，利用ZINC对接数据库对2335个新的类似物进行了计算机筛选，并选择了九个预测的候选物进行合成。这些化合物是在O中制备的-过苯甲酰化形式，可通过N-苄基-亚芳基羧酰亚胺基氯化物对5-β- d-吡喃葡萄糖基四唑进行环转化，将C-（β- d-吡喃葡萄糖基）甲酰胺ami与芳酰氯进行闭环，或将N-（β- d-吡喃葡糖基羰基）芳硫基羧酰胺通过肼，然后脱保护。针对兔肌肉
• Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production
  作者：István Kacsir、Adrienn Sipos、Gyula Ujlaki、Péter Buglyó、László Somsák、Péter Bai、Éva Bokor

  DOI：10.3390/ijms221910454

  日期：——

  Ruthenium complexes are developed as substitutes for platinum complexes to be used in the chemotherapy of hematological and gynecological malignancies, such as ovarian cancer. We synthesized and screened 14 ruthenium half-sandwich complexes with bidentate monosaccharide ligands in ovarian cancer cell models. Four complexes were cytostatic, but not cytotoxic on A2780 and ID8 cells. The IC50 values were

  钌配合物被开发为铂配合物的替代品，用于血液和妇科恶性肿瘤（如卵巢癌）的化疗。我们在卵巢癌细胞模型中合成并筛选了 14 种具有双齿单糖配体的钌半夹心配合物。四种复合物是细胞抑制性的，但对 A2780 和 ID8 细胞没有细胞毒性。IC 50值在低微摩尔范围内（最佳为 0.87 µM）并且与临床可用的铂配合物相似或低于这些值。活性复合物在胶质母细胞瘤、乳腺癌和胰腺癌的细胞模型中具有细胞抑制作用，而在未转化的人皮肤成纤维细胞上则没有细胞抑制作用。生物活性钌配合物显示出与尚未确定的细胞靶点的协同结合，并且它们的活性取决于活性氧的产生。生物活性需要糖部分羟基上的大疏水保护基团。钌配合物的细胞抑制活性取决于活性物质的产生。Rucaparib 是一种 PARP 抑制剂，可增强钌配合物的作用。