9-(2-deoxy-2-fluoro-3-O-tetrahydropyranyl-β-D-arabinofuranosyl)adenine | 192137-99-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-(2-deoxy-2-fluoro-3-O-tetrahydropyranyl-β-D-arabinofuranosyl)adenine
• 英文别名: [(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-4-fluoro-3-(oxan-2-yloxy)oxolan-2-yl]methanol
• CAS: 192137-99-8
• 化学式: C₁₅H₂₀FN₅O₄
• 分子量: 353.353
• InChiKey: FYVHKAUZGGMXDJ-ZVEUHBLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-(2-deoxy-2-fluoro-3-O-tetrahydropyranyl-β-D-arabinofuranosyl)adenine 在 吡啶 作用下， 以 二甲基亚砜 为溶剂， 反应 2.5h， 生成 9-(2-deoxy-2-fluoro-3-O-tetrahydropyranyl-β-D-arabinofuranos-5-yl)adenyl methylenebis(phosphonate)
  参考文献：
  名称：

  Synthesis of Nonhydrolyzable Analogues of Thiazole-4-carboxamide and Benzamide Adenine Dinucleotide Containing Fluorine Atom at the C2‘ of Adenine Nucleoside: Induction of K562 Differentiation and Inosine Monophosphate Dehydrogenase Inhibitory Activity

  摘要：

  Thiazole-4-carboxamide adenine dinucleotide (TAD) analogue 7 containing a fluorine atom at the C2' arabino configuration of the adenine nucleoside moiety was found to be a potent inducer of differentiation of K562 erythroid leukemia cells. This finding prompted us to synthesize its hydrolysis-resistant methylenebis(phosphonate) and difluoromethylenebis(phosphonate) analogues 8 and 9, respectively. Since both TAD and benzamide adenine dinucleotide (BAD) are potent inhibitors of inosine monophosphate dehydrogenase (IMPDH), the corresponding fluorine-substituted methylenebis(phosphonate) analogue 12 of BAD was also synthesized. Thus, 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (13) was converted in five steps into the corresponding methylenebis( phosphonate) analogue 18. Dehydration of 18 with DCC led to the formation of the bicyclic trisanhydride intermediate 19a, which upon reaction with 2',3'-O-isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12, respectively. The similar displacement of the 5'-mesyl function of 2',3'-O-isopropylidene-5'-O-mesyltiazofuin (24) with the difluoromethylenebis(phosphonic acid) derivative gave the phosphonate 25 which was coupled with 13 to afford 26. The desired difluoromethylenebis (phosphonate) analogue 9 was obtained by deprotection with Dowex 50/H+. This compound as well as beta-CF2-TAD (4) showed improved differentiation-inducing activity over beta-CH2-TAD (3), whereas analogues containing the -CH2- linkage (8 and 12) were inactive.

  DOI：

  10.1021/jm970247f
• 作为产物：
  描述：

  6-amino-9-<5-O-(tert-butyldimethylsilyl)-2-deoxy-2-fluoro-β-D-arabinofuranosyl>-9H-purine 在 对甲苯磺酸 、 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 9-(2-deoxy-2-fluoro-3-O-tetrahydropyranyl-β-D-arabinofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of Nonhydrolyzable Analogues of Thiazole-4-carboxamide and Benzamide Adenine Dinucleotide Containing Fluorine Atom at the C2‘ of Adenine Nucleoside: Induction of K562 Differentiation and Inosine Monophosphate Dehydrogenase Inhibitory Activity

  摘要：

  Thiazole-4-carboxamide adenine dinucleotide (TAD) analogue 7 containing a fluorine atom at the C2' arabino configuration of the adenine nucleoside moiety was found to be a potent inducer of differentiation of K562 erythroid leukemia cells. This finding prompted us to synthesize its hydrolysis-resistant methylenebis(phosphonate) and difluoromethylenebis(phosphonate) analogues 8 and 9, respectively. Since both TAD and benzamide adenine dinucleotide (BAD) are potent inhibitors of inosine monophosphate dehydrogenase (IMPDH), the corresponding fluorine-substituted methylenebis(phosphonate) analogue 12 of BAD was also synthesized. Thus, 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (13) was converted in five steps into the corresponding methylenebis( phosphonate) analogue 18. Dehydration of 18 with DCC led to the formation of the bicyclic trisanhydride intermediate 19a, which upon reaction with 2',3'-O-isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12, respectively. The similar displacement of the 5'-mesyl function of 2',3'-O-isopropylidene-5'-O-mesyltiazofuin (24) with the difluoromethylenebis(phosphonic acid) derivative gave the phosphonate 25 which was coupled with 13 to afford 26. The desired difluoromethylenebis (phosphonate) analogue 9 was obtained by deprotection with Dowex 50/H+. This compound as well as beta-CF2-TAD (4) showed improved differentiation-inducing activity over beta-CH2-TAD (3), whereas analogues containing the -CH2- linkage (8 and 12) were inactive.

  DOI：

  10.1021/jm970247f

文献信息

• Synthesis of Nonhydrolyzable Analogues of Thiazole-4-carboxamide and Benzamide Adenine Dinucleotide Containing Fluorine Atom at the C2‘ of Adenine Nucleoside: Induction of K562 Differentiation and Inosine Monophosphate Dehydrogenase Inhibitory Activity
  作者：Krystyna Lesiak、Kyoichi A. Watanabe、Alokes Majumdar、Michael Seidman、Kristen Vanderveen、Barry M. Goldstein、Krzysztof W. Pankiewicz

  DOI：10.1021/jm970247f

  日期：1997.8.1

  Thiazole-4-carboxamide adenine dinucleotide (TAD) analogue 7 containing a fluorine atom at the C2' arabino configuration of the adenine nucleoside moiety was found to be a potent inducer of differentiation of K562 erythroid leukemia cells. This finding prompted us to synthesize its hydrolysis-resistant methylenebis(phosphonate) and difluoromethylenebis(phosphonate) analogues 8 and 9, respectively. Since both TAD and benzamide adenine dinucleotide (BAD) are potent inhibitors of inosine monophosphate dehydrogenase (IMPDH), the corresponding fluorine-substituted methylenebis(phosphonate) analogue 12 of BAD was also synthesized. Thus, 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (13) was converted in five steps into the corresponding methylenebis( phosphonate) analogue 18. Dehydration of 18 with DCC led to the formation of the bicyclic trisanhydride intermediate 19a, which upon reaction with 2',3'-O-isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12, respectively. The similar displacement of the 5'-mesyl function of 2',3'-O-isopropylidene-5'-O-mesyltiazofuin (24) with the difluoromethylenebis(phosphonic acid) derivative gave the phosphonate 25 which was coupled with 13 to afford 26. The desired difluoromethylenebis (phosphonate) analogue 9 was obtained by deprotection with Dowex 50/H+. This compound as well as beta-CF2-TAD (4) showed improved differentiation-inducing activity over beta-CH2-TAD (3), whereas analogues containing the -CH2- linkage (8 and 12) were inactive.