O,9-bis(trimethylsilyl)-N²-acetylguanine | 54187-52-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: O,9-bis(trimethylsilyl)-N²-acetylguanine
• 英文别名: bistrimethylsilyl-N²-acetylguanine；N-(9-trimethylsilyl-6-trimethylsilyloxypurin-2-yl)acetamide
• CAS: 54187-52-9
• 化学式: C₁₃H₂₃N₅O₂Si₂
• 分子量: 337.529
• InChiKey: VNFKFFPGZIGQBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O,9-bis(trimethylsilyl)-N²-acetylguanine 在 氨 、 四氯化锡 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 122.0h， 生成 9-(6'-deoxy-β-D-allofuranosyl)guanine
  参考文献：
  名称：

  Synthesis of hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose

  摘要：

  Hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose have been prepared as potential antitumor agents. Thus, reaction of 6-deoxy-beta-D-allofuranosyl bromide (1) with the trimethylsilyl derivatives of hypoxanthine and guanine afforded mixtures of the 9- and the 7-substituted bases, which were separated and deblocked with ammonia to give 9-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (6), 7-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (7), 9-(6'-deoxy-beta-D-allofuranosyl)guanine (8), and 7-(6'-deoxy-beta-D-allofuranosyl)guanine (9). The two nucleosides with the purine joined at the N-9 position, namely, 6 and 8, are easily distinguished from the other two nucleosides (7 and 9), having N-7 junctions, by their NMR spectra. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 10, which upon treatment with thiourea and deblocking gave 9-(6'-deoxy-beta-D-allofuranosyl)-6-thiopurine (12). The hypoxanthine and guanine nucleosides showed no inhibition of mouse leukemia L1210 when tested in vivo, but the thiopurine nucleoside 12 showed strong inhibition of growth of L1210 both in vivo and in vitro. Compound 7 strongly inhibited purine nucleoside phosphorylase (KI = 8.8 X 10(-5) M), while compounds 8, 9, 6, and 12 were inactive.

  DOI：

  10.1021/jm00361a023
• 作为产物：
  描述：

  N²-acetylguanine 、 六甲基二硅氮烷 生成 O,9-bis(trimethylsilyl)-N²-acetylguanine
  参考文献：
  名称：

  Synthesis of hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose

  摘要：

  Hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose have been prepared as potential antitumor agents. Thus, reaction of 6-deoxy-beta-D-allofuranosyl bromide (1) with the trimethylsilyl derivatives of hypoxanthine and guanine afforded mixtures of the 9- and the 7-substituted bases, which were separated and deblocked with ammonia to give 9-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (6), 7-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (7), 9-(6'-deoxy-beta-D-allofuranosyl)guanine (8), and 7-(6'-deoxy-beta-D-allofuranosyl)guanine (9). The two nucleosides with the purine joined at the N-9 position, namely, 6 and 8, are easily distinguished from the other two nucleosides (7 and 9), having N-7 junctions, by their NMR spectra. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 10, which upon treatment with thiourea and deblocking gave 9-(6'-deoxy-beta-D-allofuranosyl)-6-thiopurine (12). The hypoxanthine and guanine nucleosides showed no inhibition of mouse leukemia L1210 when tested in vivo, but the thiopurine nucleoside 12 showed strong inhibition of growth of L1210 both in vivo and in vitro. Compound 7 strongly inhibited purine nucleoside phosphorylase (KI = 8.8 X 10(-5) M), while compounds 8, 9, 6, and 12 were inactive.

  DOI：

  10.1021/jm00361a023

文献信息

• Studies on griseolic acid derivatives. VII. Synthesis and phosphodiesterase inhibitory activity of the C4' - C5' hydrogenated products of griseolic acid and their base-exchanged derivatives.
  作者：YOSHINOBU MUROFUSHI、MISAKO KIMURA、HARUMITSU KUWANO、YASUTERU IIJIMA、MITSUO YAMAZAKI、MASAKATSU KANEKO

  DOI：10.1248/cpb.36.3760

  日期：——

  Addition reactions of the C4'-C5' double bond of griseolic acid were investigated. C4'-C5' Dihydrogriseolic acid was obtained by reduction of the adduct having halogen at the 4'-position. The ring juncture of the two five-membered rings of the C4'-C5' dihydro derivatives was of all- “cis” configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1'-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C4'-C5' cis dihydrogriseolic acid derivative was weaker than that of griseolic acid. The uracil derivative of C4'-C5' cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C4'-C5' trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.

  研究了灰苏氨酸 C4'-C5' 双键的加成反应。通过还原 4'- 位上含有卤素的加合物，得到了 C4'-C5' 二氢麦角苷酸。C4'-C5' 二氢衍生物的两个五元环的环连接处为全 "顺 "构型。对受保护的二氢甘草次苷酸进行乙酰分解，可得到相应的 1'- 乙酰氧基糖衍生物。将这种糖衍生物与硅烷化碱基反应，可得到二氢草胆酸的鸟嘌呤和尿嘧啶衍生物。C4'-C5' 顺式二氢麦角苷酸衍生物的环核苷酸磷酸二酯酶（PDE）抑制活性弱于麦角苷酸。C4'-C5' 顺式二氢草胆酸的尿嘧啶衍生物完全丧失了对 3'，5'-环单磷酸腺苷（cAMP）和 3'，5'-环单磷酸鸟苷（cGMP）PDE 的抑制活性，而鸟嘌呤衍生物对 cAMP PDE 的抑制活性有所降低，但对 cGMP PDE 的抑制活性保持不变。同样明显的是，从石杉酸的同一培养液中作为次要产物获得的 C4'-C5' 反式二氢衍生物与石杉酸具有几乎相同的抑制活性。
• MIKHAILOPULO, IGOR A.;POOPEIKO, NIKOLAI E.;PRICOTA, TAMARA I.;SIVETS, GRI+, J. MED. CHEM., 34,(1991) N, C. 2195-2202
  作者：MIKHAILOPULO, IGOR A.、POOPEIKO, NIKOLAI E.、PRICOTA, TAMARA I.、SIVETS, GRI+

  DOI：——

  日期：——
• MUROFUSHI, YOSHINOBU;KIMURA, MISAKO;KUWANO, HARUMITSU;IIJIMA, YASUTERU;YA+, 14TH SYMP. NUCL. ACIDS CHEM., TOKUSHIMA, OCT. 30TH - NOV. 1ST, 1986, OXFO+
  作者：MUROFUSHI, YOSHINOBU、KIMURA, MISAKO、KUWANO, HARUMITSU、IIJIMA, YASUTERU、YA+

  DOI：——

  日期：——