4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tert-butyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one | 1613293-12-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tert-butyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
• CAS: 1613293-12-1
• 化学式: C₁₉H₂₇F₂N₃O₆Si
• 分子量: 459.522
• InChiKey: VJTCAIMBRMCMNM-BPLDGKMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  111.91
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tert-butyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
  参考文献：
  名称：

  Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine

  摘要：

  Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

  DOI：

  10.1021/jm500531z
• 作为产物：
  描述：

  盐酸吉西他滨 在 吡啶 、 咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tert-butyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
  参考文献：
  名称：

  Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine

  摘要：

  Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

  DOI：

  10.1021/jm500531z