(8R)-6-(tert-Butoxycarbonyl)-8-<(tert-butyldimethylsilyl)oxy>-3,6,7,8-tetrahydroimidazo<4,5-d><1,3>diazepine | 151256-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑二氮卓类
• 英文名称: (8R)-6-(tert-Butoxycarbonyl)-8-<(tert-butyldimethylsilyl)oxy>-3,6,7,8-tetrahydroimidazo<4,5-d><1,3>diazepine
• 英文别名: (8R)-6-(tert-butoxycarbonyl)-8-(tert-butyldimethylsilyloxy)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepine；(8R)-6-(tert-butoxycarbonyl)-8-[(tert-butyldimethylsilyl)oxy]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepine；(8R)-6-(tert-butoxycarbonyl)-8-(tert-butyldimethylsilyloxy)-3,6,7,8-tetrahydro-imidazo[4,5-d][1,3]diazepine；tert-butyl (8R)-8-[tert-butyl(dimethyl)silyl]oxy-7,8-dihydro-1H-imidazo[4,5-d][1,3]diazepine-6-carboxylate
• CAS: 151256-48-3
• 化学式: C₁₇H₃₀N₄O₃Si
• 分子量: 366.536
• InChiKey: FJOSGXXYLGULHA-GFCCVEGCSA-N

物化性质

• 沸点：
  460.8±55.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.38
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (8R)-6-(tert-Butoxycarbonyl)-8-<(tert-butyldimethylsilyl)oxy>-3,6,7,8-tetrahydroimidazo<4,5-d><1,3>diazepine 在 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 8-(R)-3-(2,3-di-O-acetyl-5-S-methyl-5-thio-β-D-ribofuranosyl)-6-tert-butoxycarbonyl-8-hydroxy-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepine
  参考文献：
  名称：

  5'-甲硫基共甲霉素的合成：疟疾腺苷脱氨酶的特异性抑制剂

  摘要：

  过渡态理论表明，酶促速率加速 (kcat/knon) 与给定反应的过渡态稳定有关。预计过渡态复合物的化学稳定类似物可将催化能转化为结合能。由于过渡态稳定性是催化效率的函数，因此可以在紧密结合的过渡态类似物抑制剂的设计中利用底物特异性的差异。Coformycin 和 2'-deoxycoformycin 是腺苷脱氨酶 (ADA) 的天然产物过渡态类似物抑制剂。这些化合物模拟 ADA 过渡态的四面体几何形状，并以皮摩尔解离常数与来自牛、人类和原生动物来源的酶结合。疟疾寄生虫中嘌呤补救途径的独特之处在于恶性疟原虫 ADA (PfADA) 催化腺苷和 5'-甲基硫腺苷的脱氨基作用。相比之下，人类腺苷脱氨酶 (HsADA) 和牛酶 (BtADA) 都不能使 5'-甲基硫腺苷脱氨。5'-Methylthiocoformycin 和 5'-methylthio-2'-deoxycoformycin 被合

  DOI：

  10.1021/ja0708363
• 作为产物：
  描述：

  5-Amino-4-<(1'R)-<(2'-azido-1'-tert-butyldimethylsilyl)oxy>ethyl>-1-(2'-cyanoethyl)imidazole 在 1,3-丙二硫醇 、 5A molecular sieve 、 potassium tert-butylate 、 三乙胺 、 三氟乙酸 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.02h， 生成 (8R)-6-(tert-Butoxycarbonyl)-8-<(tert-butyldimethylsilyl)oxy>-3,6,7,8-tetrahydroimidazo<4,5-d><1,3>diazepine
  参考文献：
  名称：

  Chirospecific synthesis of the tetrahydroimidazodiazepinol aglycon of pentostatin and its analogs

  摘要：

  A high-yield, versatile method is presented for the stereo- and regiospecific synthesis of the aglycon of pentostatin and its analogues using the L-vinylglycine 1 as the chiral educt. From this four-carbon asymmetric core, containing the contiguous carbons of the target ring system, the synthetic process proceeds with development of the R absolute stereochemistry for the hydroxyl group at C-8 and nitrogen or potential nitrogen functions at the other three carbons. Conversion of the alpha-amino ester to an alpha-amino nitrile is followed by formation of the 1,4,5-trisubstituted aminoimidazole. After generating another amine by reduction of an azide, the diazepine is then annealed by treatment with orthoformate. Using this process, a series of (8R)-8-hydroxy-substituted tetrahydroimidazodiazepinols has been prepared. The protecting group protocol allows specific deprotection at N-3 for subsequent glycosylation and other substitution.

  DOI：

  10.1021/jo00074a041

文献信息

• Analogues of Coformycin and Their Use for Treating Protozoan Parasite Infections
  申请人：Furneaux Richard Hubert

  公开号：US20090227532A1

  公开（公告）日：2009-09-10

  This invention relates to compounds that are analogues of coformycin, pharmaceutical compositions containing the compounds, and methods of using the compounds for treating protozoan parasite infections, especially malaria.

  本发明涉及与可福霉素类似的化合物、包含这些化合物的制药组合物以及使用这些化合物治疗原虫寄生虫感染，尤其是疟疾的方法。
• Analogues of coformycin and their use for treating protozoan parasite infections
  申请人：Furneaux Richard Hubert

  公开号：US08394950B2

  公开（公告）日：2013-03-12

  This invention relates to compounds that are analogues of coformycin, pharmaceutical compositions containing the compounds, and methods of using the compounds for treating protozoan parasite infections, especially malaria.

  本发明涉及与Coformycin类似的化合物，包含该化合物的制药组合物，以及使用该化合物治疗原虫寄生虫感染，尤其是疟疾的方法。
• WO2007/97643
  申请人：——

  公开号：——

  公开（公告）日：——
• Chirospecific synthesis of the tetrahydroimidazodiazepinol aglycon of pentostatin and its analogs
  作者：Thien Van Truong、Henry Rapoport

  DOI：10.1021/jo00074a041

  日期：1993.10

  A high-yield, versatile method is presented for the stereo- and regiospecific synthesis of the aglycon of pentostatin and its analogues using the L-vinylglycine 1 as the chiral educt. From this four-carbon asymmetric core, containing the contiguous carbons of the target ring system, the synthetic process proceeds with development of the R absolute stereochemistry for the hydroxyl group at C-8 and nitrogen or potential nitrogen functions at the other three carbons. Conversion of the alpha-amino ester to an alpha-amino nitrile is followed by formation of the 1,4,5-trisubstituted aminoimidazole. After generating another amine by reduction of an azide, the diazepine is then annealed by treatment with orthoformate. Using this process, a series of (8R)-8-hydroxy-substituted tetrahydroimidazodiazepinols has been prepared. The protecting group protocol allows specific deprotection at N-3 for subsequent glycosylation and other substitution.
• Synthesis of 5‘-Methylthio Coformycins:  Specific Inhibitors for Malarial Adenosine Deaminase
  作者：Peter C. Tyler、Erika A. Taylor、Richard F. G. Fröhlich、Vern L. Schramm

  DOI：10.1021/ja0708363

  日期：2007.5.1

  state analogue inhibitors of adenosine deaminases (ADAs). These compounds mimic the tetrahedral geometry of the ADA transition state and bind with picomolar dissociation constants to enzymes from bovine, human, and protozoan sources. The purine salvage pathway in malaria parasites is unique in that Plasmodium falciparum ADA (PfADA) catalyzes the deamination of both adenosine and 5'-methylthioadenosine

  过渡态理论表明，酶促速率加速 (kcat/knon) 与给定反应的过渡态稳定有关。预计过渡态复合物的化学稳定类似物可将催化能转化为结合能。由于过渡态稳定性是催化效率的函数，因此可以在紧密结合的过渡态类似物抑制剂的设计中利用底物特异性的差异。Coformycin 和 2'-deoxycoformycin 是腺苷脱氨酶 (ADA) 的天然产物过渡态类似物抑制剂。这些化合物模拟 ADA 过渡态的四面体几何形状，并以皮摩尔解离常数与来自牛、人类和原生动物来源的酶结合。疟疾寄生虫中嘌呤补救途径的独特之处在于恶性疟原虫 ADA (PfADA) 催化腺苷和 5'-甲基硫腺苷的脱氨基作用。相比之下，人类腺苷脱氨酶 (HsADA) 和牛酶 (BtADA) 都不能使 5'-甲基硫腺苷脱氨。5'-Methylthiocoformycin 和 5'-methylthio-2'-deoxycoformycin 被合