D-mannaro-1,4:6,3-dilactone | 654072-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: D-mannaro-1,4:6,3-dilactone
• 英文别名: D-Idosaccharodilacton；(3S,3aS,6S,6aS)-3,6-dihydroxy-3,3a,6,6a-tetrahydrofuro[3,2-b]furan-2,5-dione
• CAS: 654072-11-4
• 化学式: C₆H₆O₆
• 分子量: 174.11
• InChiKey: QRFNDAVXJCGLFB-LDHWTSMMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甘露醇 在 硝酸 作用下， 以 水 为溶剂， 反应 4.75h， 以11%的产率得到D-mannaro-1,4:6,3-dilactone
  参考文献：
  名称：

  Hydroxyl Stereochemistry and Amine Number within Poly(glycoamidoamine)s Affect Intracellular DNA Delivery

  摘要：

  Nucleic acid drugs have great potential to treat many devastating aliments, but their application has been hindered by the lack of efficacious and nontoxic delivery vehicles. Here, a new library of poly(glycoamidoamine)s (D1 -D4, G1 -G4, and M1 -M4) has been synthesized by polycondensation of esterified D-glucaric acid (D), dimethyl-meso-galactarate (G), and (D)-mannaro-1,4:6,3-dilactone (M) with diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4). The stereochemistry of the carbohydrate hydroxyl groups and the number of amine units have been systematically changed in an effort to examine how the polymer chemistry affects the plasmid DNA (pDNA) binding affinity, the compaction of pDNA into nanoparticles (polyplexes), the material cytotoxicity, and the efficacy of nucleic acid delivery. The polymers with four secondary amines (D4, G4, and M4) between the carbohydrates were found to have the highest pDNA binding affinity and the galactarate polymers generally yielded the smallest polyplexes. Delivery studies with pDNA containing the firefly luciferase or beta-galactosidase reporter genes in BHK-21, HeLa, and HepG2 cells demonstrated that all of the poly(glycoamicloamine)s deliver pDNA without cytotoxicity. Polymers D4, G4, and M4 displayed the highest delivery efficiency, where G4 was found to be a particularly effective delivery vehicle. Heparin competition assays indicated that this may be a result of the higher pDNA binding affinity displayed by G4 as compared to D4 and M4. Polyplexes formed by polymers with weaker pDNA affinities may dissociate at the cell surface due to interactions with negatively charged glycosaminoglycans, which would cause a decrease in the number of polyplexes that are enclocytosed.

  DOI：

  10.1021/ja0436446

文献信息

• 2,3,4,5-TETRAHYDROXYHEXANDISÄUREESTER AUS DILACTONEN DER 2,3,4,5-TETRAHYDROXYHEXANDISÄURE
  申请人：BASF SE

  公开号：EP3258909B1

  公开（公告）日：2019-09-25
• Hydroxyl Stereochemistry and Amine Number within Poly(glycoamidoamine)s Affect Intracellular DNA Delivery
  作者：Yemin Liu、Theresa M. Reineke

  DOI：10.1021/ja0436446

  日期：2005.3.9

  Nucleic acid drugs have great potential to treat many devastating aliments, but their application has been hindered by the lack of efficacious and nontoxic delivery vehicles. Here, a new library of poly(glycoamidoamine)s (D1 -D4, G1 -G4, and M1 -M4) has been synthesized by polycondensation of esterified D-glucaric acid (D), dimethyl-meso-galactarate (G), and (D)-mannaro-1,4:6,3-dilactone (M) with diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4). The stereochemistry of the carbohydrate hydroxyl groups and the number of amine units have been systematically changed in an effort to examine how the polymer chemistry affects the plasmid DNA (pDNA) binding affinity, the compaction of pDNA into nanoparticles (polyplexes), the material cytotoxicity, and the efficacy of nucleic acid delivery. The polymers with four secondary amines (D4, G4, and M4) between the carbohydrates were found to have the highest pDNA binding affinity and the galactarate polymers generally yielded the smallest polyplexes. Delivery studies with pDNA containing the firefly luciferase or beta-galactosidase reporter genes in BHK-21, HeLa, and HepG2 cells demonstrated that all of the poly(glycoamicloamine)s deliver pDNA without cytotoxicity. Polymers D4, G4, and M4 displayed the highest delivery efficiency, where G4 was found to be a particularly effective delivery vehicle. Heparin competition assays indicated that this may be a result of the higher pDNA binding affinity displayed by G4 as compared to D4 and M4. Polyplexes formed by polymers with weaker pDNA affinities may dissociate at the cell surface due to interactions with negatively charged glycosaminoglycans, which would cause a decrease in the number of polyplexes that are enclocytosed.