[acetyl(methyl)amino]methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | 51164-31-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: [acetyl(methyl)amino]methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 51164-31-9
• 化学式: C₂₀H₂₅N₃O₅S
• 分子量: 419.502
• InChiKey: JPSBAUSHBNIZLA-SOLBZPMBSA-N

物化性质

• 沸点：
  685.2±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [acetyl(methyl)amino]methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 在 phosphate buffer 作用下， 生成 penicillin G
  参考文献：
  名称：

  A new direct synthesis of tertiary N-acyloxymethylamide prodrugs of carboxylic acid drugs

  摘要：

  N-Alkyl-N-chloromethylamides 2, prepared from secondary amides, paraformaldehyde and chlorotrimethylsilane, react readily with carboxylate anions to generate the corresponding tertiary N-acyloxymethylamides 3 in good yield; the latter give rise to the parent carboxylic acids in aqueous media at pH 7.4 and 37 degrees C with half-lives between ca. 1 min and 42 h.

  DOI：

  10.1016/0040-4039(94)88238-x
• 作为产物：
  描述：

  N-氯甲基-N-甲基乙酰胺 、 Penicillin G sodium 以 四氢呋喃 为溶剂， 以56%的产率得到[acetyl(methyl)amino]methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
  参考文献：
  名称：

  A new direct synthesis of tertiary N-acyloxymethylamide prodrugs of carboxylic acid drugs

  摘要：

  N-Alkyl-N-chloromethylamides 2, prepared from secondary amides, paraformaldehyde and chlorotrimethylsilane, react readily with carboxylate anions to generate the corresponding tertiary N-acyloxymethylamides 3 in good yield; the latter give rise to the parent carboxylic acids in aqueous media at pH 7.4 and 37 degrees C with half-lives between ca. 1 min and 42 h.

  DOI：

  10.1016/0040-4039(94)88238-x

文献信息

• ——
  作者：Rui Moreira、Teresa Calheiros、José Cabrita、Eduarda Mendes、Madalena Pimentel、Jim Iley

  DOI：10.1023/a:1016077200460

  日期：——

  indicating that beta-lactam ring opening is much slower than ester hydrolysis. The O-(N-alkylamido)methyl esters of penicillin G displayed similar in vitro antibacterial activity to penicillin G itself. CONCLUSIONS Compared to the penicillin G derivatives, the much higher stability of the O-(N-methylbenzamido)methyl benzoate, acetate and valproate esters (which gave rise to a Bronsted Beta 1g value of ca. -1)

  研究了青霉素G的目的O-（N-烷基氨基）甲基酯作为一类新的前药。方法通过HPLC研究了在含有20％（v / v）乙腈的水性缓冲液中的水解。结果观察到一个U形pH速率分布，其pH值独立于pH值的过程。pH值约为2。10.该途径的特点是动力学数据与涉及限速亚胺离子形成和青霉素排出的单分子机理相一致。青霉素G和相应的酰胺是检测到并分离出的最终产物，表明β-内酰胺开环比酯水解慢得多。青霉素G的O-（N-烷基酰胺基）甲基酯显示出与青霉素G相似的体外抗菌活性。结论与青霉素G衍生物相比，
• A new direct synthesis of tertiary N-acyloxymethylamide prodrugs of carboxylic acid drugs
  作者：Rui Moreira、Eduarda Mendes、Teresa Calheiros、Maria J. Bacelo、Jim Iley

  DOI：10.1016/0040-4039(94)88238-x

  日期：1994.9

  N-Alkyl-N-chloromethylamides 2, prepared from secondary amides, paraformaldehyde and chlorotrimethylsilane, react readily with carboxylate anions to generate the corresponding tertiary N-acyloxymethylamides 3 in good yield; the latter give rise to the parent carboxylic acids in aqueous media at pH 7.4 and 37 degrees C with half-lives between ca. 1 min and 42 h.