(1S,2S,3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid | 367250-83-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (1S,2S,3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid
• 英文别名: (1S,2S,3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxycycloheptane-1-carboxylic acid
• CAS: 367250-83-7
• 化学式: C₂₃H₂₅NO₅
• 分子量: 395.455
• InChiKey: PQFDRPBULNPNGQ-TYPHKJRUSA-N

物化性质

• 沸点：
  648.6±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

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 、 (1S,2S,3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-cycloheptanecarboxylic acid 、 2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid 、 alkaline earth salt of/the/ methylsulfuric acid 以1.51 mg的产率得到2-[2-[2-[[(2S,3R)-2-[[(1S,2S,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,2S,3S,4'S)-[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 (1S,2S,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

文献信息

• Analogues of Bleomycin:  Synthesis of Conformationally Rigid Methylvalerates
  作者：Michael J. Rishel、Sidney M. Hecht

  DOI：10.1021/ol010139u

  日期：2001.9.1

  Several conformationally rigid analogues of the methylvalerate subunit contained within the linker domain of the antitumor antibiotic bleomycin have been prepared. These compounds have been protected in a fashion suitable for the solid-phase synthesis of bleomycin. Bleomycin congeners containing these analogues should facilitate a more detailed understanding of the nature of the conformational bend that

  [结构：见文字]。已经制备了抗肿瘤抗生素博来霉素的接头域内所含的几种戊酸甲酯亚基的构象刚性类似物。这些化合物已经以适用于博来霉素固相合成的方式得到了保护。含有这些类似物的博来霉素同类物应有助于更详细地理解认为戊酸甲酯部分赋予天然产物的构象弯曲的性质。