7-amino-3-<3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-(phenoxythiocarbonyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine | 96807-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 7-amino-3-<3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-(phenoxythiocarbonyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine
• 英文别名: 7-amino-3-<3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2-(phenoxythiocarbonyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine；7-amino-3-[3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-(phenoxythiocarbonyl)-β-D-ribofuranosyl]pyrazolo[4,3-d]pyrimidine；[(6aR,8S,9S,9aR)-8-(7-amino-2H-pyrazolo[4,3-d]pyrimidin-3-yl)-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-yl]oxy-phenoxymethanethione
• CAS: 96807-06-6
• 化学式: C₂₉H₄₃N₅O₆SSi₂
• 分子量: 645.927
• InChiKey: UFPNTFZZKGUXLR-ORZNUPDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.08
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  168
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  7-amino-3-<3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-(phenoxythiocarbonyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine 在 吡啶 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 7.0h， 生成 7-N-benzoylamino-3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrazolo<4,3-d>pyrimidine
  参考文献：
  名称：

  Synthesis of Triple Helix Forming Oligonucleotides Containing 2′-Deoxyformycin A

  摘要：

  N-7-Benzoyl-2'-deoxyformycin A ((5) under bar) was prepared from formycin A and incorporated into the triple helix forming oligonucleotide PRE2ap at CG inversion sites. The modified oligonucleotide containing three substitutions of 2'-deoxyformycin A displayed a 10-fold increase in binding affinity as compared to its unmodified counterpart. This provided a method to accommodate CG inversion sites within target sites for antiparallel triple helix formation.

  DOI：

  10.1080/15257779408013229
• 作为产物：
  描述：

  formycin 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 乙腈 为溶剂， 反应 10.5h， 生成 7-amino-3-<3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-(phenoxythiocarbonyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine
  参考文献：
  名称：

  Synthesis of Triple Helix Forming Oligonucleotides Containing 2′-Deoxyformycin A

  摘要：

  N-7-Benzoyl-2'-deoxyformycin A ((5) under bar) was prepared from formycin A and incorporated into the triple helix forming oligonucleotide PRE2ap at CG inversion sites. The modified oligonucleotide containing three substitutions of 2'-deoxyformycin A displayed a 10-fold increase in binding affinity as compared to its unmodified counterpart. This provided a method to accommodate CG inversion sites within target sites for antiparallel triple helix formation.

  DOI：

  10.1080/15257779408013229

文献信息

• Improved synthesis of 2'-deoxyformycin A and studies of its in vitro activity against mouse lymphoma of T-cell origin
  作者：Andre Rosowsky、Vishnu C. Solan、Lorraine J. Gudas

  DOI：10.1021/jm00146a020

  日期：1985.8

  7-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (2'-deoxyformycin A) was synthesized from formycin A by a sequence consisting of (i) 3',5'-cyclosilylation with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, (ii) 2'-acylation with phenoxythiocarbonyl chloride and 4-(N,N-dimethylamino)pyridine, (iii) N-trimethylsilylation with hexamethyldisilazane, (iv) reduction of the 2'-O-phenoxythiocarbonyl group with tri-n-butyltin hydride, and (v) desilylation with tetra-n-butylammonium fluoride. 2'-Deoxyformycin A was a potent inhibitor of the in vitro growth of S49 lymphoma, a murine tumor of T-cell origin. The IC50 of 2'-deoxyformycin A against S49 cells was 10-15 microM, whereas that of 2'-deoxyadenosine (dAdo) under the same conditions (72-h incubation in medium containing heat-inactivated horse serum) was 180 microM. In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM. When assayed against a mutant S49 subline lacking adenosine kinase (AK) or a subline with a combined deletion of AK and deoxycytidine kinase (dCK), 2'-deoxyformycin A in combination with 10 microM EHNA was inactive at concentrations of up to 50 microM. Similar lack of activity against kinase-deficient cells was shown by formycin A. Thus, phosphorylation of 2'-deoxyformycin A appears to be required for biological activity and is probably catalyzed by AK rather than dCK. 2'-Deoxyformycin A and related 2'-deoxyribo-C-nucleoside analogues of the purine type may be of interest as potential T-cell specific cytotoxic agents.
• Efficient Synthesis of 2'-Deoxyformycin A Containing Oligonucleotides and Characterization of Their Stability in Duplex DNA
  作者：Heiko Kuhn、David P. Smith、Sheila S. David

  DOI：10.1021/jo00127a010

  日期：1995.11
• Synthesis of Triple Helix Forming Oligonucleotides Containing 2′-Deoxyformycin A
  作者：T. Sudhakar Rao、Michael E. Hogan、Ganapathi R. Revankar

  DOI：10.1080/15257779408013229

  日期：1994.3

  N-7-Benzoyl-2'-deoxyformycin A ((5) under bar) was prepared from formycin A and incorporated into the triple helix forming oligonucleotide PRE2ap at CG inversion sites. The modified oligonucleotide containing three substitutions of 2'-deoxyformycin A displayed a 10-fold increase in binding affinity as compared to its unmodified counterpart. This provided a method to accommodate CG inversion sites within target sites for antiparallel triple helix formation.