(4Z,8E)-7-Hydroxy-8-methyl-9-(2-methyl-thiazol-4-yl)-nona-4,8-dienethioic acid S-(2-acetylamino-ethyl) ester | 722547-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4Z,8E)-7-Hydroxy-8-methyl-9-(2-methyl-thiazol-4-yl)-nona-4,8-dienethioic acid S-(2-acetylamino-ethyl) ester
• CAS: 722547-26-4
• 化学式: C₁₈H₂₆N₂O₃S₂
• 分子量: 382.548
• InChiKey: KEXVYUNFUXDXGL-DISXHPKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  25.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.29
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  丙酸钠-1-13C 、 (4Z,8E)-7-Hydroxy-8-methyl-9-(2-methyl-thiazol-4-yl)-nona-4,8-dienethioic acid S-(2-acetylamino-ethyl) ester 在 E_. coli strain BAP₁ 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Precursor-Directed Biosynthesis of Epothilone in Escherichia coli

  摘要：

  Engineered biosynthetic pathways provide a powerful method for generating complex molecules. Precursor-directed biosynthesis, which combines chemical synthesis and enzymatic transformations, allows non-native starting materials to be incorporated into biosynthetic pathways. Using this approach, we achieved the production of the anticancer agent epothilone C in Escherichia coli. An E. coli strain was engineered to express the last three modules of the epothilone biosynthetic pathway (epoD-M6, epoE, and epoF) and the substrate required to complement the biosynthetic enzymes was obtained by chemical synthesis. Under high-density cell culture conditions, the E. coli strain processed exogenously fed synthetic substrate into epothilone C at levels comparable to the native host (1 mg/L) and at higher levels than other heterologous hosts. Importantly, this precursor-directed approach will allow chemical modifications to be introduced into the polyketide backbone and may ultimately provide access to epothilone analogues with improved pharmacological properties in quantities sufficient for clinical development.

  DOI：

  10.1021/ja048108s
• 作为产物：
  描述：

  (4Z,8E)-7-Hydroxy-8-methyl-9-(2-methyl-thiazol-4-yl)-nona-4,8-dienoic acid ethyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (4Z,8E)-7-Hydroxy-8-methyl-9-(2-methyl-thiazol-4-yl)-nona-4,8-dienethioic acid S-(2-acetylamino-ethyl) ester
  参考文献：
  名称：

  Precursor-Directed Biosynthesis of Epothilone in Escherichia coli

  摘要：

  Engineered biosynthetic pathways provide a powerful method for generating complex molecules. Precursor-directed biosynthesis, which combines chemical synthesis and enzymatic transformations, allows non-native starting materials to be incorporated into biosynthetic pathways. Using this approach, we achieved the production of the anticancer agent epothilone C in Escherichia coli. An E. coli strain was engineered to express the last three modules of the epothilone biosynthetic pathway (epoD-M6, epoE, and epoF) and the substrate required to complement the biosynthetic enzymes was obtained by chemical synthesis. Under high-density cell culture conditions, the E. coli strain processed exogenously fed synthetic substrate into epothilone C at levels comparable to the native host (1 mg/L) and at higher levels than other heterologous hosts. Importantly, this precursor-directed approach will allow chemical modifications to be introduced into the polyketide backbone and may ultimately provide access to epothilone analogues with improved pharmacological properties in quantities sufficient for clinical development.

  DOI：

  10.1021/ja048108s