oxo-tomaymycin | 35050-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: oxo-tomaymycin
• 英文别名: (6aS)-8-ethylidene-3-hydroxy-2-methoxy-5,6a,7,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepine-6,11-dione
• CAS: 35050-54-5
• 化学式: C₁₅H₁₆N₂O₄
• 分子量: 288.303
• InChiKey: KXUMNEWSLYWWIA-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-酪氨酸 、 L-色氨酸 反应 45.0h， 生成 11-de-O-methyltomaymycin 、 oxo-tomaymycin
  参考文献：
  名称：

  Biosynthesis of [ ¹⁴ C]‐11‐De‐ O ‐Methyltomaymycin, a Precursor of Radiolabelled Antibody Drug Conjugates

  摘要：

  AbstractAntibody drug conjugates (ADCs) are one of the most promising technologies to treat cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as tomaymycin derivatives, which are DNA‐interactive antitumor antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some tomaymycin derivatives is complicated because their structures contain a reactive imine bond. Therefore, we turned to biosynthesis to obtain 14C radiolabelled tomaymycin derivative to support ADME studies. Following Hurley's work (J. Antibiotics 1977, 30, 349–370; Antimicrob. Agents Chemother. 1979, 15, 42–45; Acc. Chem. Res. 1980, 13, 263–269), the 14C radiolabel was incorporated efficiently in one step from radiolabelled tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.

  DOI：

  10.1002/cbic.202100080

文献信息

• Biosynthesis of [ ¹⁴ C]‐11‐De‐ <i>O</i> ‐Methyltomaymycin, a Precursor of Radiolabelled Antibody Drug Conjugates
  作者：Catherine Aubert、Mélanie Lavisse、Sebastien Roy

  DOI：10.1002/cbic.202100080

  日期：2021.7.15

  AbstractAntibody drug conjugates (ADCs) are one of the most promising technologies to treat cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as tomaymycin derivatives, which are DNA‐interactive antitumor antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some tomaymycin derivatives is complicated because their structures contain a reactive imine bond. Therefore, we turned to biosynthesis to obtain 14C radiolabelled tomaymycin derivative to support ADME studies. Following Hurley's work (J. Antibiotics 1977, 30, 349–370; Antimicrob. Agents Chemother. 1979, 15, 42–45; Acc. Chem. Res. 1980, 13, 263–269), the 14C radiolabel was incorporated efficiently in one step from radiolabelled tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.