methyl 2-benzyloxycarbonylamino-2-deoxy-α/β-D-glucopyranoside | 57089-81-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-benzyloxycarbonylamino-2-deoxy-α/β-D-glucopyranoside
• 英文别名: methyl 2-deoxy-2-(N-benzyloxycarbonylamino)-D-glucopyranoside；methyl-2-(N-benzyloxycarbonyl)amino-2-deoxyl-D-glucoside；Methyl-2-benzyloxycarbonyl-amino-2-deoxy-αβ-D-glucopyranosid；1-O-Methyl-N-benzyloxycarbonyl-D-glucosamin；benzyl N-[(3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]carbamate
• CAS: 57089-81-3
• 化学式: C₁₅H₂₁NO₇
• 分子量: 327.334
• InChiKey: MXCBPGJIPRBQAE-GNMOMJPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-benzyloxycarbonylamino-2-deoxy-α/β-D-glucopyranoside 在 盐酸 、 sodium tetrahydroborate 、 silver cyanide 作用下， 以 吡啶 、 甲醇 、 乙醇 为溶剂， 反应 73.5h， 生成 [(1S,2R,3S,4R)-5-(Diethoxy-phosphoryloxy)-2,3,4-trihydroxy-1-hydroxymethyl-pentyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Hydrophobic derivatives of 2-amino-2-deoxy-d-glucitol-6-phosphate: A new type of d-Glucosamine-6-phosphate synthase inhibitors with antifungal action

  摘要：

  Several N-acyl and ester derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) have been synthesised and tested as inhibitors of fungal enzymes involved in early steps of chitin biosynthesis and for antifungal activity. All the tested derivatives were found to be much poorer inhibitors of the enzyme, D-glucosamine-6-phosphate (GIcN-6-P) synthase, than the parent compound but some of them exhibited much better antifungal activity. MIC values for the investigated compounds ranged between 10 mg mL(-1), found for ADGP and 0.3 mg mL(-1) for the most active derivative, namely ADGP dimethyl ester. Increased affinity of ADGP derivatives to the artificial immobilised cell membrane was correlated with their enhanced ability to be taken up by fungal cells by free diffusion. It was found that some of the examined derivatives behaved as 'pro-drugs' and after internalisation were converted into ADGP in the cell-free extract. This conversion was relatively rapid for ADGP esters but very slow for N-acyl derivatives. Results of our studies demonstrate a possibility of design and preparation of GIcN-6-P synthase inhibitors exhibiting antifungal activity. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00049-x
• 作为产物：
  描述：

  2-氨基-2-脱氧葡萄糖盐酸盐 在 碳酸氢钠 、 对甲苯磺酸 作用下， 以 甲醇 、 水 为溶剂， 反应 66.0h， 生成 methyl 2-benzyloxycarbonylamino-2-deoxy-α/β-D-glucopyranoside
  参考文献：
  名称：

  Effects of Cholesterol on the Miscibility of Synthetic Glucosamine Diesters in Lipid Bilayers and the Entrapment of Superoxide Dismutase into the Positively Charged Liposomes.

  摘要：

  甲基-D-葡萄糖胺-3,6-二月桂酰、二肉豆蔻酰、二棕榈酰或二硬脂酰酯被合成作为带正电的脂质。它们被结合到磷脂酰胆碱脂质体膜中，并尝试将超氧化物歧化酶（SOD）包封到脂质体中。将胆固醇添加到膜中，可以提高SOD包封效率到由蛋黄磷脂酰胆碱和合成葡萄糖胺二酯组成的带正电的多层囊泡（MLVs）中。差示扫描量热法研究表明，随着膜中胆固醇的加入，葡萄糖胺二酯在磷脂酰胆碱双层中的混溶性（溶解度）增加。胆固醇有助于磷脂酰胆碱与带正电的葡萄糖胺二酯的混合，并增加了脂质体膜上的正电荷。随着胆固醇含量的增加，脂质体膜的zeta电位逐渐增加，这一结论被证实。因此，由于带正电的膜与带负电的SOD之间的静电吸引增强，或带正电的膜之间的静电斥力增强，SOD的包封变得更加有效；后一种相互作用导致MLVs中的水层增厚。

  DOI：

  10.1248/cpb.41.1889

文献信息

• Effects of Cholesterol on the Miscibility of Synthetic Glucosamine Diesters in Lipid Bilayers and the Entrapment of Superoxide Dismutase into the Positively Charged Liposomes.
  作者：Koichiro MIYAJIMA、Hiroaki KOMATSU、Changqi SUN、Hiromitsu AOKI、Tetsurou HANDA、Haijian XU、Kaoru FUJI、Satoshi OKADA

  DOI：10.1248/cpb.41.1889

  日期：——

  Methyl-D-glucosamine-3, 6-dilauroyl, dimyristoyl, dipalmitoyl or distearoyl esters were synthesized as positively charged lipids. They were incorporated into phosphatidylcholine liposomal membranes and the entrapment of superoxide dismutase (SOD) into the liposomes was attempted. The efficiency of the SOD-entrapment into the positively charged multilamellar vesicles (MLVs), comprising egg yolk phosphatidylcholine and synthetic glucosamine diesters, was enhanced by the addition of cholesterol to the membranes. A differential scanning calorimetric study showed that the miscibility (solubility) of glucosamine diesters in phosphatidylcholine-bilayers increased on the addition of cholesterol to the membranes. Cholesterol assisted in the mixing of phosphatidylcholines with positively charged glucosamine diesters and increased the positive charges on the liposomal membranes. This was confirmed by incremental increases in the zeta-potential of liposomal membranes with an increase in the cholesterol content. Entrapment of SOD thus became more efficient due to the enhanced electrostatic attraction between the positvely charged membranes and the negatively charged SOD, and/or the electrostatic repulsive interactions between positiviely charged membranes; the latter interactions induced a thickening of the water layer in MLVs.

  甲基-D-葡萄糖胺-3,6-二月桂酰、二肉豆蔻酰、二棕榈酰或二硬脂酰酯被合成作为带正电的脂质。它们被结合到磷脂酰胆碱脂质体膜中，并尝试将超氧化物歧化酶（SOD）包封到脂质体中。将胆固醇添加到膜中，可以提高SOD包封效率到由蛋黄磷脂酰胆碱和合成葡萄糖胺二酯组成的带正电的多层囊泡（MLVs）中。差示扫描量热法研究表明，随着膜中胆固醇的加入，葡萄糖胺二酯在磷脂酰胆碱双层中的混溶性（溶解度）增加。胆固醇有助于磷脂酰胆碱与带正电的葡萄糖胺二酯的混合，并增加了脂质体膜上的正电荷。随着胆固醇含量的增加，脂质体膜的zeta电位逐渐增加，这一结论被证实。因此，由于带正电的膜与带负电的SOD之间的静电吸引增强，或带正电的膜之间的静电斥力增强，SOD的包封变得更加有效；后一种相互作用导致MLVs中的水层增厚。
• Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography
  作者：Kenji Arimitsu、Yusuke Yagi、Kazuhiro Koshino、Yukina Nishito、Takahiro Higuchi、Hiroyuki Yasui、Hiroyuki Kimura

  DOI：10.1016/j.bmcl.2020.127400

  日期：2020.9

  for in-vivo GLUT2 imaging. Fluorine was introduced to hexyl groups at the 3′-positions of the compounds, and we aimed to synthesize compounds that were more stable than STZ. The nitroso derivatives exhibited relatively good stability during purification and purity analysis after radiosynthesis. We then evaluated the compounds in PET imaging and ex-vivo biodistribution studies. We observed high levels

  葡萄糖转运蛋白2（GLUT2）参与肝细胞，胰脏β细胞和肾小肠及肾小管中的吸收性细胞的葡萄糖吸收。胰腺GLUT2在葡萄糖刺激的胰岛素分泌机制中也起着重要作用。在这项研究中，新型的Fluorine-18标记的链脲佐菌素（STZ）衍生物被合成为体内GLUT2成像的糖苷类似物。将氟引入到化合物3'-位置的己基上，我们的目标是合成比STZ更稳定的化合物。亚硝基衍生物在放射合成后的纯化和纯度分析过程中表现出相对较好的稳定性。然后，我们评估了PET成像和离体成像中的化合物生物分布研究。我们观察到肝和肾中高水平的放射性，这表明在给药5分钟内这些器官中积累了放射性。相反，脱亚硝基衍生物仅在给药后不久在肾脏和膀胱中积累。因此，具有亚硝基的化合物有望在表达GLUT2的器官中积累，亚硝基的存在对于体内GLUT2成像至关重要。
• ADAM, S., TETRAHEDRON LETT., 29,(1988) N 50, C. 6589-6592
  作者：ADAM, S.

  DOI：——

  日期：——
• Huemmer, Walter; Dubois, Eric; Gracza, Tibor, Synthesis, 1997, # 6, p. 634 - 642
  作者：Huemmer, Walter、Dubois, Eric、Gracza, Tibor、Jaeger, Volker

  DOI：——

  日期：——
• Hydrophobic derivatives of 2-amino-2-deoxy-d-glucitol-6-phosphate: A new type of d-Glucosamine-6-phosphate synthase inhibitors with antifungal action
  作者：Agnieszka M Janiak、Maria Hoffmann、Maria J Milewska、Sławomir Milewski

  DOI：10.1016/s0968-0896(03)00049-x

  日期：2003.4

  Several N-acyl and ester derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) have been synthesised and tested as inhibitors of fungal enzymes involved in early steps of chitin biosynthesis and for antifungal activity. All the tested derivatives were found to be much poorer inhibitors of the enzyme, D-glucosamine-6-phosphate (GIcN-6-P) synthase, than the parent compound but some of them exhibited much better antifungal activity. MIC values for the investigated compounds ranged between 10 mg mL(-1), found for ADGP and 0.3 mg mL(-1) for the most active derivative, namely ADGP dimethyl ester. Increased affinity of ADGP derivatives to the artificial immobilised cell membrane was correlated with their enhanced ability to be taken up by fungal cells by free diffusion. It was found that some of the examined derivatives behaved as 'pro-drugs' and after internalisation were converted into ADGP in the cell-free extract. This conversion was relatively rapid for ADGP esters but very slow for N-acyl derivatives. Results of our studies demonstrate a possibility of design and preparation of GIcN-6-P synthase inhibitors exhibiting antifungal activity. (C) 2003 Elsevier Science Ltd. All rights reserved.