hexa-tert-butyl <4-<<(2-amino-3-cyanopyrazin-5-yl)methyl>amino>benzoyl>-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate | 133042-50-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: hexa-tert-butyl <4-<<(2-amino-3-cyanopyrazin-5-yl)methyl>amino>benzoyl>-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate
• 英文别名: ditert-butyl (2S)-2-[[(4S)-4-[[(4S)-4-[[(4S)-4-[[(4S)-4-[[4-[(5-amino-6-cyanopyrazin-2-yl)methylamino]benzoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]pentanedioate
• CAS: 133042-50-9
• 化学式: C₆₂H₉₄N₁₀O₁₇
• 分子量: 1251.49
• InChiKey: RVDMYLAWEALWOW-ZSDKEGLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  89.0
• 可旋转键数：
  29.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  390.92
• 氢给体数：
  7.0
• 氢受体数：
  22.0

反应信息

• 作为反应物：
  描述：

  乙酸乙脒 、 hexa-tert-butyl <4-<<(2-amino-3-cyanopyrazin-5-yl)methyl>amino>benzoyl>-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate 以 乙二醇甲醚 为溶剂， 反应 1.75h， 以64%的产率得到hexa-tert-butyl <4-<<(4-amino-2-methylpteridin-6-yl)methyl>amino>benzoyl>-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate
  参考文献：
  名称：

  First use of the Taylor pteridine synthesis as a route to polyglutamate derivatives of antifolates

  摘要：

  The di- through penta-gamma-L-glutamates of 2-desamino-2-methylaminopterin, a new antifolate with a novel mechanism of action requiring gamma-polyglutamylation for biological activity, were prepared. alpha-tert-Butyl gamma-methyl L-glutamate was condensed with 4-nitrobenzoyl chloride, the methyl ester selectively hydrolyzed with base, and the product condensed with di-tert-butyl L-glutamate to obtain tri-tert-butyl N-(4-nitrobenzoyl)-gamma-L-glutamyl-L-glutamate. Reduction of the nitro group followed by reaction with 2-amino-5-(chloromethyl)-pyrazine-3-carbonitrile yielded tri-tert-butyl [4-[[(2-amino-3-cyanopyrazin-5-yl)methyl]amino]benzoyl]-L-gamma-glutamyl-L-glutamate, which was heated with acetamidine acetate to form tri-tert-butyl N-[4-[[(4-amino-2-methylpteridine-6-yl)methyl]amino]benzoyl]-gamma-L-glutamyl-L-glutamate. Removal of the ester groups with trifluoroacetic acid then gave 2-desamino-2-methylaminopterin diglutamate. A similar sequence was employed to convert esterified oligomers with three, four, and five glutamyl residues to 2-desamino-2-methylaminopterin tri-, tetra-, and pentaglutamate. This is the first example of the preparation of the polyglutamates of an antifolate via the Taylor pteridine synthesis.

  DOI：

  10.1021/jo00010a038
• 作为产物：
  描述：

  hexa-tert-butyl N-(4-aminobenzoyl)-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate 、 3-氨基-6-(氯甲基)吡嗪甲腈 以24%的产率得到
  参考文献：
  名称：

  BADER, HENRY;ROSOWSKY, ANDRE, J. ORG. CHEM., 56,(1991) N0, C. 3386-3391

  摘要：

  DOI：