3,5-O-(R)-benzylidene-6-cyano-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose | 136839-36-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,5-O-(R)-benzylidene-6-cyano-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose
• 英文别名: 2-[(1S,2R,6R,8R,9R,11R)-4,4-dimethyl-11-phenyl-3,5,7,10,12-pentaoxatricyclo[6.4.0.02,6]dodecan-9-yl]acetonitrile
• CAS: 136839-36-6
• 化学式: C₁₇H₁₉NO₅
• 分子量: 317.342
• InChiKey: AKVJFRRZWDGACU-BKQXGZDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.26
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  69.94
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3,5-O-(R)-benzylidene-6-cyano-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose 在 吡啶 、 sodium tetrahydroborate 、 二异丁基氢化铝 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.25h， 生成 3,5-O-(R)-benzylidene-6-deoxy-1,2-O-isopropylidene-7-O-(4-methylbenzenesulfonyl)-α-D-gluco-hepto-1,4-furanose
  参考文献：
  名称：

  Synthesis and evaluation of glucose-ADP hybrids as inhibitors of hexokinase

  摘要：

  Glucose-ADP hybrids, in which carboxamide (4) and linear acetylene (5) and allene (6) functional groups link the two moieties, were designed as potential multisubstrate analogue inhibitors for hexokinase. The diastereomeric aldehydes 15 and 28 were key intermediates in the synthesis of these compounds. Reduction of 15, amination, and acylation with (diethylphosphono)acetic acid provided the amide phosphonate 20. Reduction of 15, three-carbon extension to the propargylic bromide 25, and Arbuzov displacement gave the acetylenic phosphonate 26. Addition of ethynylmagnesium bromide to aldehyde 28, separation of the diastereomers, and Mark rearrangement afforded the allenic phosphonates 31R and 31S. Cleavage of the phosphonate esters (trimethylsilyl bromide) and acetal hydrolysis (90% aqueous trifluoroacetic acid) furnished the corresponding deprotected phosphonic acids, which were coupled with adenosine 5'-monophosphate through activation with carbonyl di(imidazole). Inhibition of yeast hexokinase by carboxamide 4 (K(i) = 0.2 mM) and acetylene 5 (K(i) = 2.5 mM) is competitive with glucose and noncompetitive with ATP; the R-allene 6R (IC50 = 1.7 mM) and S-allene 6S (IC50 = 10 mM) are also weak inhibitors. It was concluded that these compounds are not functioning as multisubstrate analogues. The beta,gamma-methylene-gamma-methylthio analogue of ATP (7) was also synthesized. This compound in combination with glucose, as well as gamma-thio-ATP (9) in combination with 6-deoxy-6-iodoglucose (8), were investigated for potential enzyme-induced, covalent coupling. No evidence for such coupling was observed.

  DOI：

  10.1021/jo00025a033
• 作为产物：
  描述：

  氰化四丁基铵 、 3,5-O-(S)-benzylidene-6-deoxy-6-iodo-1,2-O-isopropylidene-α-D-glucofuranose 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以84%的产率得到3,5-O-(R)-benzylidene-6-cyano-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose
  参考文献：
  名称：

  Synthesis and evaluation of glucose-ADP hybrids as inhibitors of hexokinase

  摘要：

  Glucose-ADP hybrids, in which carboxamide (4) and linear acetylene (5) and allene (6) functional groups link the two moieties, were designed as potential multisubstrate analogue inhibitors for hexokinase. The diastereomeric aldehydes 15 and 28 were key intermediates in the synthesis of these compounds. Reduction of 15, amination, and acylation with (diethylphosphono)acetic acid provided the amide phosphonate 20. Reduction of 15, three-carbon extension to the propargylic bromide 25, and Arbuzov displacement gave the acetylenic phosphonate 26. Addition of ethynylmagnesium bromide to aldehyde 28, separation of the diastereomers, and Mark rearrangement afforded the allenic phosphonates 31R and 31S. Cleavage of the phosphonate esters (trimethylsilyl bromide) and acetal hydrolysis (90% aqueous trifluoroacetic acid) furnished the corresponding deprotected phosphonic acids, which were coupled with adenosine 5'-monophosphate through activation with carbonyl di(imidazole). Inhibition of yeast hexokinase by carboxamide 4 (K(i) = 0.2 mM) and acetylene 5 (K(i) = 2.5 mM) is competitive with glucose and noncompetitive with ATP; the R-allene 6R (IC50 = 1.7 mM) and S-allene 6S (IC50 = 10 mM) are also weak inhibitors. It was concluded that these compounds are not functioning as multisubstrate analogues. The beta,gamma-methylene-gamma-methylthio analogue of ATP (7) was also synthesized. This compound in combination with glucose, as well as gamma-thio-ATP (9) in combination with 6-deoxy-6-iodoglucose (8), were investigated for potential enzyme-induced, covalent coupling. No evidence for such coupling was observed.

  DOI：

  10.1021/jo00025a033