(1R,2R,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid | 367250-84-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (1R,2R,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid
• 英文别名: (1R,2R,3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxycycloheptane-1-carboxylic acid
• CAS: 367250-84-8
• 化学式: C₂₃H₂₅NO₅
• 分子量: 395.455
• InChiKey: PQFDRPBULNPNGQ-HMXCVIKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-Thr-OH 、 pyrimidoblamic acid 、 2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid 、 (1R,2R,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid 、 alkaline earth salt of/the/ methylsulfuric acid 以1.49 mg的产率得到2-[2-[2-[[(2S,3R)-2-[[(1R,2R,3R)-3-[[(2S,3R)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-hydroxy-3-(1H-imidazol-5-yl)propanoyl]amino]-2-hydroxycycloheptanecarbonyl]amino]-3-hydroxybutanoyl]amino]ethyl]-1,3-thiazol-4-yl]-N-[3-(4-aminobutylamino)propyl]-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Conformationally Constrained Analogues of Bleomycin A₅

  摘要：

  The bleomycin (BLM) group antitumor antibiotics are glycopeptide-derived natural products shown to cause sequence selective lesions in DNA. Prior studies have indicated that the linker region, composed of the methylvalerate and threonine residues, may be responsible for a conformational bend in the agent required for efficient DNA cleavage. We have synthesized a number of conformationally constrained methylvalerate analogues and incorporated them into deglycobleomycin A(5) congeners using our recently reported procedure for the solid phase construction of (deglyco)bleomycin and its analogues. These analogues were designed to probe the effects of conformational constraint of the native valerate moiety. Initial experiments indicated that the constrained molecules, none of which mimic the conformation proposed for the natural valerate linker, possessed DNA cleavage activity, albeit with potencies less than that of (deglyco)BLM and lacking sequence selectivity. Further experiments demonstrated that these analogues failed to produce alkali-labile lesions in DNA or sequence selective oxidative damage in RNA. However, two of the conformationally constrained deglycoBLM analogues were shown to mediate RNA cleavage in the absence of added Fe2+. The ability of the analogues to mediate the oxygenation of small molecules was also assayed, and it was shown that they were as competent in the transfer of oxygen to low molecular weight substrates as the parent compound.

  DOI：

  10.1021/ja030057w
• 作为产物：
  描述：

  (1R,2R,3R,4'R)-[1-allyl-2-hydroxy-3-(4'-isopropyl-2'-oxo-oxazolidine-3'-carbonyl)-hex-5-enyl]-carbamic acid tert-butyl ester 在 platinum on activated charcoal lithium hydroxide 、 Grubbs catalyst first generation 、 二甲基硫 、 氢气 、 双氧水 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 96.0h， 生成 (1R,2R,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid
  参考文献：
  名称：

  Conformationally Constrained Analogues of Bleomycin A₅

  摘要：

  The bleomycin (BLM) group antitumor antibiotics are glycopeptide-derived natural products shown to cause sequence selective lesions in DNA. Prior studies have indicated that the linker region, composed of the methylvalerate and threonine residues, may be responsible for a conformational bend in the agent required for efficient DNA cleavage. We have synthesized a number of conformationally constrained methylvalerate analogues and incorporated them into deglycobleomycin A(5) congeners using our recently reported procedure for the solid phase construction of (deglyco)bleomycin and its analogues. These analogues were designed to probe the effects of conformational constraint of the native valerate moiety. Initial experiments indicated that the constrained molecules, none of which mimic the conformation proposed for the natural valerate linker, possessed DNA cleavage activity, albeit with potencies less than that of (deglyco)BLM and lacking sequence selectivity. Further experiments demonstrated that these analogues failed to produce alkali-labile lesions in DNA or sequence selective oxidative damage in RNA. However, two of the conformationally constrained deglycoBLM analogues were shown to mediate RNA cleavage in the absence of added Fe2+. The ability of the analogues to mediate the oxygenation of small molecules was also assayed, and it was shown that they were as competent in the transfer of oxygen to low molecular weight substrates as the parent compound.

  DOI：

  10.1021/ja030057w