1-cinnamoyl-3-tert-butyldimethylsilylchloramphenicol | 2232888-91-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1-cinnamoyl-3-tert-butyldimethylsilylchloramphenicol
• 英文别名: 2-Propenoic acid, 3-phenyl-, (1R,2R)-2-[(2,2-dichloroacetyl)amino]-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-(4-nitrophenyl)propyl ester, (2E)-；[(1R,2R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(2,2-dichloroacetyl)amino]-1-(4-nitrophenyl)propyl] (E)-3-phenylprop-2-enoate
• CAS: 2232888-91-2
• 化学式: C₂₆H₃₂Cl₂N₂O₆Si
• 分子量: 567.541
• InChiKey: JMCREMQGFRJIAR-ZQATUQSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  37.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107.77
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-cinnamoyl-3-tert-butyldimethylsilylchloramphenicol 在 对甲苯磺酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以85%的产率得到1-cinnamoylchloramphenicol
  参考文献：
  名称：

  Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics

  摘要：

  A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acety1-3-butanoyl-chloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 mu g/mL, respectively.

  DOI：

  10.1021/acs.jnatprod.7b00903
• 作为产物：
  描述：

  氯霉素 在 吡啶 、 咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-cinnamoyl-3-tert-butyldimethylsilylchloramphenicol
  参考文献：
  名称：

  Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics

  摘要：

  A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acety1-3-butanoyl-chloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 mu g/mL, respectively.

  DOI：

  10.1021/acs.jnatprod.7b00903