((2R,3R,4S,5R)-3-(benzoyloxy)-5-(2,6-diazido-9H-purin-9-yl)-4-fluorotetrahydrofuran-2-yl)methyl benzoate | 1013918-32-5

• 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: ((2R,3R,4S,5R)-3-(benzoyloxy)-5-(2,6-diazido-9H-purin-9-yl)-4-fluorotetrahydrofuran-2-yl)methyl benzoate
• CAS: 1013918-32-5
• 化学式: C₂₄H₁₇FN₁₀O₅
• 分子量: 544.461
• InChiKey: NAHKKHJFDBBRHS-VWFIUDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  202.95
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  ((2R,3R,4S,5R)-3-(benzoyloxy)-5-(2,6-diazido-9H-purin-9-yl)-4-fluorotetrahydrofuran-2-yl)methyl benzoate 在 adenosine deaminase E_.C_. 3.5.4.4 a 、 氨 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 9-(2-脱氧-2-氟阿拉伯呋喃基)鸟嘌呤
  参考文献：
  名称：

  Oligonucleotides Containing 9-(2-Deoxy-2-Fluoro-β-D-Arabinofuranosyl)-Adenine and -Guanine: Synthesis, Hybridization and Antisense Properties

  摘要：

  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.

  DOI：

  10.1080/15257770008045466
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 叠氮化锂 、 三氟甲磺酸三甲基硅酯 、 六甲基二硅氮烷 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 23.33h， 生成 ((2R,3R,4S,5R)-3-(benzoyloxy)-5-(2,6-diazido-9H-purin-9-yl)-4-fluorotetrahydrofuran-2-yl)methyl benzoate
  参考文献：
  名称：

  Oligonucleotides Containing 9-(2-Deoxy-2-Fluoro-β-D-Arabinofuranosyl)-Adenine and -Guanine: Synthesis, Hybridization and Antisense Properties

  摘要：

  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.

  DOI：

  10.1080/15257770008045466

文献信息

• Synthesis and anti-HIV activity of 2′-fluorine modified nucleoside phosphonates: Analogs of GS-9148
  作者：Richard L. Mackman、Kuei-Ying Lin、Constantine G. Boojamra、Hon Hui、Janet Douglas、Deborah Grant、Oleg Petrakovsky、Vidya Prasad、Adrian S. Ray、Tomas Cihlar

  DOI：10.1016/j.bmcl.2007.11.126

  日期：2008.2

  Modified purine analogs of GS-9148 [5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (2'-Fd4AP) were synthesized and their anti-HIV potency evaluated. The antiviral activity of guanosine analog (2'-Fd4GP) was comparable that of to 2'-Fd4AP in MT-2 cells, but selectivity was reduced.

  合成了GS-9148 [5-（6-氨基-嘌呤-9-基）-4-氟-2,5-二氢呋喃-2-基氧基甲基]-膦酸（2'-Fd4AP）的修饰嘌呤类似物，他们的抗艾滋病毒效力进行了评估。鸟嘌呤类似物（2'-Fd4GP）的抗病毒活性与MT-2细胞中2'-Fd4AP的抗病毒活性相当，但选择性降低。