9-(2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine | 20187-82-0

• 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-α-D-arabinofuranosyl)adenine
• 英文别名: 1-(6-amino-purin-9-yl)-2-fluoro-α-D-1,2-dideoxy-arabinofuranose；9-(2-fluoro-α-D-arabinosyl)adenine；(2R,3R,4S,5S)-5-(6-Amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3R,4S,5S)-5-(6-aminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• CAS: 20187-82-0
• 化学式: C₁₀H₁₂FN₅O₃
• 分子量: 269.235
• InChiKey: ZGYYPTJWJBEXBC-ASTPYSOASA-N

物化性质

• 沸点：
  628.6±65.0 °C(Predicted)
• 密度：
  2.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  9-Trimethylsilanyl-9H-purin-6-ylamine 在 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 68.0h， 生成 9-(2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine
  参考文献：
  名称：

  Striking Ability of Adenosine-2′(3′)-deoxy-3′(2′)-triphosphates and Related Analogues to Replace ATP as Phosphate Donor for All Four Human, and theDrosophila Melanogaster, Deoxyribonucleoside Kinases

  摘要：

  In extension of an earlier report, six non-conventional analogues of ATP, three adenosine-2'-triphosphates (3'-deoxy, 3'-deoxy-3'-fluoro- and 3'-deoxy-3'-fluoroxylo-), and three adenosine-3'-triphosphates (2'-deoxy-, 2'-deoxy-2'-fluoro- and 2'-deoxy-2'-fluoroara-), were compared with ATP as potential phosphate donors for human deoxycytidine kinase (dCK), cytosolic thymidine kinase (TK1), mitochondrial TK2, deoxyguanosine kinase (dGK), and the deoxyribonucleoside kinase (dNK) from Drosophila melanogaster. With one group of enzymes, comprising TK1, TK2, dNK and dCK (with dAdo as acceptor), only 3'-deoxyadenosine-2'-triphosphate was an effective donor (5-60% that for ATP), and the other five analogues much less so, or inactive. With a second set, including dCK (dCyd, but not dAdo, as acceptor) and dGK (dGuo as acceptor), known to share high sequence similarity (approximate to 45% sequence identity), all six analogues were good to excellent donors (13-119% that for ATP). With dCK and ATP1, products were shown to be 5'-phosphates. With dCK, donor properties of the analogues were dependent on the nature of the acceptor, as with natural 5'-triphosphate donors. With dCK (dCyd as acceptor), K-m and V-max for the two 2'(3)deoxyadenosine-3'(2')-triphosphates are similar to those for ATP. With dGK, K-m values are higher than for ATP, while V-max values are comparable. Kinetic studies further demonstrated Michaelis-Menten (non-cooperative) or cooperative kinetics, dependent on the enzyme employed and the nature of the donor. The physiological significance, if any, of the foregoing remains to be elucidated. The overall results are, on the other hand, highly relevant to studies on the modes of interaction of nucleoside kinases with donors and acceptors; and, in particular, to interpretations of the recently reported crystal structures of dGK with bound ATP, of dNK with bound dCyd, and associated modeling studies.

  DOI：

  10.1081/ncn-120019510

文献信息

• EP1676853
  申请人：——

  公开号：——

  公开（公告）日：——
• Oligonucleotides Containing 9-(2-Deoxy-2-Fluoro-β-D-Arabinofuranosyl)-Adenine and -Guanine: Synthesis, Hybridization and Antisense Properties
  作者：Tuula Tennilä、Elena Azhayeva、Jouko Vepsäläinen、Reino Laatikainen、Alex Azhayev、Igor A. Mikhailopulo

  DOI：10.1080/15257770008045466

  日期：2000.10

  Synthesis of 9-(2-deoxy-2-fluoro-beta -D-arabinofuranosyl)-adenine (7, ara-A(2'F)) and -guanine (12, ara-G(2'F)) was accomplished via the condensation of 2,6-dichloropurine (1) with 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-alpha -D-arabinofuranose (2) as a key chemical step. Condensation of silylated N-6-benzoyladenine (6) with 2 gave, after deblocking and chromatographic separation, ara-A(2'F) (7) (14%), it's alpha -anomer 8 (14%) and N-7-alpha -isomer 9 (25%). The PSEUROT analysis of N-9-beta -D-arabinosides 7 and 12 manifested slight preference for the S rotamer (64%) for the former, and an equal population of the N and S rotamers for the latter. The arabinosides 7 and 12 were used for the preparation of the respective phosphoamidite building blocks 13 and 14 for automated oligonucleotide synthesis. Four 15-mer oligonucleotides (ONs) complementary to the initiation codon region of firefly luciferase mRNA were prepared: unmodified 2'-deoxy-ON (AS1) and containing (i) ara-A(2'F) instead of the only A (AS2), (ii) ara-G(2'F) vs. 3-G from the 5'-terminus (AS3), and (iii) both arabinosides at the same positions (AS4). All these ONs display practically the same (i) affinity to both complementary DNA and RNA, and (ii) ability to inhibit a luciferase gene expression in a cell-free transcription-translation system.
• Striking Ability of Adenosine-2′(3′)-deoxy-3′(2′)-triphosphates and Related Analogues to Replace ATP as Phosphate Donor for All Four Human, and the<i>Drosophila Melanogaster</i>, Deoxyribonucleoside Kinases
  作者：Krzysztof Krawiec、Borys Kierdaszuk、Elena N. Kalinichenko、Elena B. Rubinova、Igor A. Mikhailopulo、Staffan Eriksson、Birgitte Munch-Petersen、David Shugar

  DOI：10.1081/ncn-120019510

  日期：2003.5

  In extension of an earlier report, six non-conventional analogues of ATP, three adenosine-2'-triphosphates (3'-deoxy, 3'-deoxy-3'-fluoro- and 3'-deoxy-3'-fluoroxylo-), and three adenosine-3'-triphosphates (2'-deoxy-, 2'-deoxy-2'-fluoro- and 2'-deoxy-2'-fluoroara-), were compared with ATP as potential phosphate donors for human deoxycytidine kinase (dCK), cytosolic thymidine kinase (TK1), mitochondrial TK2, deoxyguanosine kinase (dGK), and the deoxyribonucleoside kinase (dNK) from Drosophila melanogaster. With one group of enzymes, comprising TK1, TK2, dNK and dCK (with dAdo as acceptor), only 3'-deoxyadenosine-2'-triphosphate was an effective donor (5-60% that for ATP), and the other five analogues much less so, or inactive. With a second set, including dCK (dCyd, but not dAdo, as acceptor) and dGK (dGuo as acceptor), known to share high sequence similarity (approximate to 45% sequence identity), all six analogues were good to excellent donors (13-119% that for ATP). With dCK and ATP1, products were shown to be 5'-phosphates. With dCK, donor properties of the analogues were dependent on the nature of the acceptor, as with natural 5'-triphosphate donors. With dCK (dCyd as acceptor), K-m and V-max for the two 2'(3)deoxyadenosine-3'(2')-triphosphates are similar to those for ATP. With dGK, K-m values are higher than for ATP, while V-max values are comparable. Kinetic studies further demonstrated Michaelis-Menten (non-cooperative) or cooperative kinetics, dependent on the enzyme employed and the nature of the donor. The physiological significance, if any, of the foregoing remains to be elucidated. The overall results are, on the other hand, highly relevant to studies on the modes of interaction of nucleoside kinases with donors and acceptors; and, in particular, to interpretations of the recently reported crystal structures of dGK with bound ATP, of dNK with bound dCyd, and associated modeling studies.