benzhydryl (6R,7R)-7-amino-3-[[4-[(3R)-3-ethyl-2,6-dioxopiperidin-3-yl]phenyl]carbamoyloxymethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 805231-37-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzhydryl (6R,7R)-7-amino-3-[[4-[(3R)-3-ethyl-2,6-dioxopiperidin-3-yl]phenyl]carbamoyloxymethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 805231-37-2
• 化学式: C₃₅H₃₄N₄O₇S
• 分子量: 654.744
• InChiKey: IKQFMHVVIGLXGW-NUMAFVGSSA-N

物化性质

• 沸点：
  839.1±65.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  182
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzhydryl (6R,7R)-7-amino-3-[[4-[(3R)-3-ethyl-2,6-dioxopiperidin-3-yl]phenyl]carbamoyloxymethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 在 三氯化铝 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 1.33h， 生成 (6R,7Z)-3-[[4-[(3R)-3-ethyl-2,6-dioxopiperidin-3-yl]phenyl]carbamoyloxymethyl]-7-[(4-methylphenyl)sulfonylamino]sulfanylimino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT

  摘要：

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.

  DOI：

  10.1021/jo048970i
• 作为产物：
  描述：

  7-氨基头孢烷酸 在 四(三苯基膦)钯 吡啶 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 ammonium sulfate 、 对甲苯亚磺酸 、 acetylesterase 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 88.17h， 生成 benzhydryl (6R,7R)-7-amino-3-[[4-[(3R)-3-ethyl-2,6-dioxopiperidin-3-yl]phenyl]carbamoyloxymethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT

  摘要：

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.

  DOI：

  10.1021/jo048970i

文献信息

• Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT
  作者：Jonathan W. Grant、Timothy P. Smyth

  DOI：10.1021/jo048970i

  日期：2004.11.1

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.