N²-isobutyryl-9-(2-fluoro-3,5-di-O-tetrahydropyran-2-yl-β-D-arabinofuranosyl)guanine | 146954-69-0

• 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: N²-isobutyryl-9-(2-fluoro-3,5-di-O-tetrahydropyran-2-yl-β-D-arabinofuranosyl)guanine
• 英文别名: N-[9-[(2R,3R,4R,5R)-3-fluoro-4-(oxan-2-yloxy)-5-(oxan-2-yloxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 146954-69-0
• 化学式: C₂₄H₃₄FN₅O₇
• 分子量: 523.562
• InChiKey: CEUGYZLXXMYLAT-DZIWGVIMSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N²-isobutyryl-9-(2-fluoro-3,5-di-O-tetrahydropyran-2-yl-β-D-arabinofuranosyl)guanine 在 吡啶 、 Dowex 50W x 2-100 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基-2'-氟脱氧鸟苷
  参考文献：
  名称：

  Uniformly modified 2'-deoxy-2'-fluoro-phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets

  摘要：

  均一化修饰的磷酸二酯或硫代磷酸酯寡核苷酸，包含2'-脱氧-2'-氟腺苷、-鸟苷、-尿苷和-胞苷，首次在此报道，当它们与RNA杂交时，表现出一致的叠加性稳定性提升，同时不会影响碱基配对的特异性。2'-脱氧-2'-氟修饰的寡核苷酸与RNA杂交的圆二色光谱表明，杂交双链呈现完全的A型构象。以磷酸二酯形式存在的2'-脱氧-2'-氟修饰的寡核苷酸对核酸酶不具抵抗力；然而，以硫代磷酸酯形式存在的修饰寡核苷酸则具有极高的核酸酶抗性，并且保留了对RNA靶标的卓越结合亲和力。2'-脱氧-2'-氟修饰对RNA-DNA双链的稳定化效果被证明优于2'-O-甲基核糖的替代。与均一化2'-脱氧-2'-氟修饰寡核苷酸形成的RNA杂交双链不支持HeLa细胞中RNase H活性；然而，将修饰引入到“嵌合”寡核苷酸中已被证明可以激活哺乳动物的RNase H。均一化修饰的2'-脱氧-2'-氟硫代磷酸酯寡核苷酸提供了反义分子，具有（1）对RNA靶标的高结合亲和力和选择性，以及（2）对核酸酶的稳定性。

  DOI：

  10.1021/jm00059a007
• 作为产物：
  描述：

  9-Β-D-糖呋喃鸟嘌呤 在 吡啶 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 sodium hydroxide 、 三甲基氯硅烷 、 四丁基氟化铵 、 对甲苯磺酸 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 生成 N²-isobutyryl-9-(2-fluoro-3,5-di-O-tetrahydropyran-2-yl-β-D-arabinofuranosyl)guanine
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of Arabinosylguanine and 2′-Deoxy-2′-Fluoro-guanosine

  摘要：

  An efficient conversion from commercially available 2,6-diaminopurine-2',3',5'-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2'-deoxy-2'-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product.

  DOI：

  10.1080/07328319708006246

文献信息

• Uniformly modified 2'-deoxy-2'-fluoro-phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets
  作者：Andrew M. Kawasaki、Martin D. Casper、Susan M. Freier、Elena A. Lesnik、Maryann C. Zounes、Lendell L. Cummins、Carolyn Gonzalez、P. Dan Cook

  DOI：10.1021/jm00059a007

  日期：1993.4

  ''Uniformly'' modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and -cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro-modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into ''chimeric'' oligonucleotides has been shown to activate mammalian RNase H. ''Uniformly'' modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases.

  均一化修饰的磷酸二酯或硫代磷酸酯寡核苷酸，包含2'-脱氧-2'-氟腺苷、-鸟苷、-尿苷和-胞苷，首次在此报道，当它们与RNA杂交时，表现出一致的叠加性稳定性提升，同时不会影响碱基配对的特异性。2'-脱氧-2'-氟修饰的寡核苷酸与RNA杂交的圆二色光谱表明，杂交双链呈现完全的A型构象。以磷酸二酯形式存在的2'-脱氧-2'-氟修饰的寡核苷酸对核酸酶不具抵抗力；然而，以硫代磷酸酯形式存在的修饰寡核苷酸则具有极高的核酸酶抗性，并且保留了对RNA靶标的卓越结合亲和力。2'-脱氧-2'-氟修饰对RNA-DNA双链的稳定化效果被证明优于2'-O-甲基核糖的替代。与均一化2'-脱氧-2'-氟修饰寡核苷酸形成的RNA杂交双链不支持HeLa细胞中RNase H活性；然而，将修饰引入到“嵌合”寡核苷酸中已被证明可以激活哺乳动物的RNase H。均一化修饰的2'-脱氧-2'-氟硫代磷酸酯寡核苷酸提供了反义分子，具有（1）对RNA靶标的高结合亲和力和选择性，以及（2）对核酸酶的稳定性。
• An Efficient and Scalable Synthesis of Arabinosylguanine and 2′-Deoxy-2′-Fluoro-guanosine
  作者：Bruce S. Ross、Robert H. Springer、Kelly G. Sprankle、Guillermo Vasquez

  DOI：10.1080/07328319708006246

  日期：1997.7

  An efficient conversion from commercially available 2,6-diaminopurine-2',3',5'-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2'-deoxy-2'-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product.